Contents
Special Issue Topic

CHOLESTASIS

Guest Editor

Prof. Jose J. G. Marin E-Mail

Head of Dept. Physiology & Pharmacology, University of Salamanca; Experimental Hepatology and Drug Targeting (HEVEPHARM); Carlos III National Institute of Health, Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd); Salamanca Institute for Biomedical Research (IBSAL); Salamanca, Spain.

Research Keywords: bile acids; cholestasis; liver and gastrointestinal cancer; chemoresistance and chemosensitization; drug targeting; gene therapy

About the Special lssue

Many liver diseases are accompanied by cholestasis, which is defined nowadays as the partial or total reduction of bile flow to the duodenum due to the lack of secretion by the liver, associated with hepatocellular and ductular functional failure, or the retention in the biliary system by obstruction at some point of the biliary tree, resulting in any event in the regurgitation into the blood of cholephilic substances, i.e., compounds typically secreted in the bile, such as bile acids and bilirubin. 

This special issue will review updated information regarding several critical aspects involving the etiology and pathophysiology of cholestasis, with a particular focus on the role of inborn errors in proteins accounting for bile acid transport and metabolism. The usefulness of bile acids and other compounds in the diagnosis and treatment of cholestasis, as well as clinical aspects of this condition, will also be reviewed. This special issue will also benefit from contributions on any additional question affecting this complex problem, from alteration in the endocrine and paracrine regulation of the biliary function to the relationship of cholestasis with cholesterol metabolism by hepatocytes and the physiological and pathological involvement of cholangiocytes and the biliary tree in the overall secretory function of the liver. Liver diseases in which cholestasis is an essential accompanying feature, such as some types of drug-induced liver injury (DILI), among others, will also have room in this special issue. Finally, another broad field of interest in cholestasis research and clinics concerns the crosstalk between the liver and gut in both directions, regarding the FXR/FGF19 pathway of communication between intestinal epithelial cells and hepatocytes and the other way around the impact of bile acids on intestinal digestive function and microbiota biology.

Keywords: Cholestasis, bile acid, bile flow, bilirubin, FXR, FGF19 Transport, metabolism

Published Articles

Open Access Review
Interplay of autophagy, apoptosis, and senescence in primary biliary cholangitis
The pathogenesis of primary biliary cholangitis (PBC) is particularly complicated as both intrinsic and extrinsic factors are implicated. Several forms of cellular death, both programmable and non-p
Published: October 16, 2023 Explor Dig Dis. 2023;2:223–245
1775 31 1
Open Access Review
Drug-induced cholestasis: causative agents and challenges in diagnosis and management
Drug-induced liver injury (DILI) is an adverse reaction to drugs and other xenobiotics that can have serious consequences and jeopardise progress in pharmacological therapy. While DILI is predominan
Published: September 18, 2023 Explor Dig Dis. 2023;2:202–222
14468 220 3
Open Access Review
Pathophysiology of biochemical signs of primary biliary cholangitis
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a rare chronic autoimmune cholestatic liver disease, affecting mostly females. With PBС develops chronic cholang
Published: August 27, 2023 Explor Dig Dis. 2023;2:149–171
3310 56 0
Open Access Case Report
Diagnostic workup of suspected hereditary cholestasis in adults: a case report
Hereditary cholestasis comprises a broad spectrum of clinical phenotypes of varying severity. Severe forms such as progressive familial intrahepatic cholestasis (PFIC) mostly affect children with di
Published: April 21, 2023 Explor Dig Dis. 2023;2:34–43
2703 86 1
Open Access Review
Monitoring the hepatobiliary function using image techniques and labeled cholephilic compounds
Evaluation of the hepatobiliary function is critical for the clinicians, not only for the diagnosis of a large variety of liver diseases but also in the follow-up and management of some patients, for instance, those with different degrees of cholestasis suffering from a drug-induced liver injury (DILI) or scheduled for liver resection. Currently, the determination of global liver function mainly relies on laboratory tests, clinical scores, and data from images obtained with ultrasonography, computed tomography (CT), or magnetic resonance. Nuclear medicine scanning, displaying either planar or three-dimensional spatial distribution of liver function, is enhanced when using hepatotropic tracers based on classical radioisotopes such as technetium-99m (99mTc) and with higher resolution using metabolized probes such as those based on monosaccharide derivatives labeled with 18F. Other cholephilic compounds, and hence selectively secreted into bile, have been proposed to visualize the correct function of the liver parenchyma and the associated secretory machinery. This review aims to summarize the state-of-the-art regarding the techniques and chemical probes available to monitor liver and gallbladder function, in some cases based on imaging techniques reflecting the dynamic of labeled cholephilic compounds.
Published: February 28, 2023 Explor Dig Dis. 2023;2:18–33
1908 45 2
Open Access Review
The bile acid receptor TGR5 and cholestasis
Metabolic zonation in the liver carries out the maintenance of organ and body homeostasis. Hypoxia is an inherent physiological feature of the liver and contributes to the zonal properties of the he
Published: December 30, 2022 Explor Dig Dis. 2022;1:154–169
2494 58 0
Open Access Review
Cholestasis associated to inborn errors in bile acid synthesis
Several metabolic pathways are involved in the biotransformation of C27 neutral cholesterol to C24 primary bile acids (BAs), mainly cholic acid (CA) and chenodeoxycholic acid (CDCA), which are then conjugated with glycine or taurine. This process can start with the modification of the steroid ring or the shortening of the side chain and involves enzymes present in different subcellular compartments. Inborn errors affecting the biogenesis of organelles, such as peroxisomes, or the expression or function of specific enzymes of these convergent routes result in: i) the lack of mature C24-BAs, with the subsequent impairment in digestion and absorption of dietary fat and liposoluble vitamins, such as vitamin K, which may account for a deficient hepatic synthesis of several coagulation factors; ii) the accumulation of intermediate metabolites, which may affect hepatocyte physiology, causing cholestasis as a commonly shared alteration besides other deleterious hepatic events; and iii) extrahepatic clinical manifestations due to accumulation of toxic metabolites in other territories, such as the nervous system, causing neurological disorders. In general, diseases whose primary alteration is a genetic defect in BA synthesis are diagnosed in children or young individuals with a very low incidence. The symptomatology can markedly vary among individuals, ranging from mild to severe conditions. Oral therapy, based on the enrichment of the BA pool with natural C24-BAs, such as CA, CDCA, glyco-CA, or ursodeoxycholic acid (UDCA), depending on the exact deficiency causing the disease, may be beneficial in preventing life-threatening situations. In contrast, in other cases, a liver transplant is the only option for these patients. This review describes the updated information on the genetic and molecular bases of these diseases and the current approaches to achieve a selective diagnosis and specific treatment.
Published: December 7, 2022 Explor Dig Dis. 2022;1:137–153
2839 85 0
Open Access Review
Etiopathogenesis and pathophysiology of cholestasis
Normal hepatobiliary function depends on an adequate bile flow from the liver through the biliary tree to the gallbladder, where bile is stored and concentrated, and from the gallbladder to the duod
Published: October 31, 2022 Explor Dig Dis. 2022;1:97–117
9920 297 2