Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We characterized the phenotypic response to UDCA based on BA and bacterial profiles of PBC patients treated with UDCA. Patients from the UK-PBC cohort (n = 419) treated with UDCA for a minimum of 12-months were assessed using the Barcelona dynamic response criteria. BAs from serum, urine, and feces were analyzed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry and fecal bacterial composition measured using 16S rRNA gene sequencing. We identified 191 non-responders, 212 responders, and a subgroup of responders with persistently elevated liver biomarkers (n = 16). Responders had higher fecal secondary and tertiary BAs than non-responders and lower urinary bile acid abundances, with the exception of 12-dehydrocholic acid, which was higher in responders. The sub-group of responders with poor liver function showed lower alpha-diversity evenness, lower abundance of fecal secondary and tertiary BAs than the other groups and lower levels of phyla with BA-deconjugation capacity (Actinobacteriota/Actinomycetota, Desulfobacterota, Verrucomicrobiota) compared to responders. UDCA dynamic response was associated with an increased capacity to generate oxo-/epimerized secondary BAs. 12-dehydrocholic acid is a potential biomarker of treatment response. Lower alpha-diversity and lower abundance of bacteria with BA deconjugation capacity might be associated with an incomplete response to treatment in some patients.

Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents.

Oxime derivatives of dehydrocholic acid and its esters were designed for anti-hepatitis B virus (HBV) drugs according to principles of assembling active chemical fragments. Twelve compounds were synthesized from dehydrocholic acid by esterification and oxime formation, and their anti-hepatitis B virus (HBV) activities were evaluated with HepG 2.2.15 cells. Results showed that 5 compounds exhibited more effective inhibition of HBeAg than positive control, among them 2b-3 and 2b-1 showed significant anti-HBV activities on inhibiting secretion of HBeAg (IC50 (2b-3) = 49.39 ± 12.78 µM, SI (2b-3) = 11.03; IC50 (2b-1) = 96.64 ± 28.99 µM, SI (2b-1) = 10.35) compared to the Entecavir (IC50 = 161.24 µM, SI = 3.72). Molecular docking studies showed that most of these compounds interacted with protein residues of heparan sulfate proteoglycan (HSPG) in host hepatocyte and bile acid receptor.

Dehydrocholic Acid Ameliorates Sodium Taurocholate-Induced Acute Biliary Pancreatitis in Mice.

Acute biliary pancreatitis (ABP) with a high mortality rate is an incurable digestive system disease induced by abnormal bile acid regurgitation due to the biliary obstruction. Dehydrocholic acid (DA) alleviates the severity of cholestatic hepatitis related to biliary inflammation, suggesting DA is potential to develop for the incurable ABP management. Here we identified DA potency and explored the underlying mechanism in ABP. Our data showed that DA administration not only reduced typically clinicopathological parameters including serum levels of amylase and lipase but also suppressed pancreatic tissue edema, necrosis and trypsin activation in ABP mice. We also found that DA significantly reduced the necrosis of pancreatic acinar cells induced by sodium taurocholate (NaT). Further experimental data showed the significant inhibitions of DA on mitochondrial membrane potential depolarization, ATP exhaustion, calcium overload and reactive oxygen species (ROS) erupted in acinar cells induced by NaT, indicating DA could avert acinar cell death through protecting the mitochondrial function, scavenging excessive oxidative stress and balancing calcium. The comprehensive study found DA elevated the expression of transcription factor EB (TFEB) in vitro thus to increase the functional lysosome content. Indeed, DA decreased the Microtubule-associated protein light chain 3 (LC3) II/I ratio as well as ubiquitin-binding protein p62 and Parkin expressions in vivo and in vitro, revealing autophagy restoration maybe through the improvement of TFEB-mediated lysosome biogenesis. These data indicate that DA improves ABP through the mitochondrial protection, antioxidant ability enhancement and autophagy recovery. In conclusion, our study proposes a potential therapy strategy for the incurable ABP.

Effect of dehydrocholic acid conjugated with a hydrocarbon on a lipid bilayer composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine.

The effects of bile acids, dehydrocholic acid (DHA) and DHA conjugated with a hydrocarbon (6-aminohexanoate; 6A-DHA) were evaluated using a lipid bilayer composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). DOPC formed a homogenous thin membrane in presence or absence of the DHA, while 20 mol% 6A-DHA induced phase separation on the DOPC thin membrane. It was observed formation of a stomatocyte-like liposomes when these membranes were suspended in a basic solvent. Generally, liposome formation can be prevented by some bile acids. It was found that DHA and 6A-DHA did not disrupt liposome formation, while DHA and 6A-DHA perturbed the liposomal membrane, resulting in increased local-fluidity due to the bent structure of DHA and 6A-DHA. DHA and 6A-DHA showed completely different effects on the hydrophobicity of the boundary surface of DOPC liposome membranes. The steroidal backbone of DHA was found to prevent the insertion of water molecules into the liposomal membrane, whereas 6A-DHA did not show the same behavior which was attributed to its conjugated hydrocarbon.

Experimental protoporphyria: effect of bile acids on liver damage induced by griseofulvin.

The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris) was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA), dehydrocholic (DHA), chenodeoxycholic, or ursodeoxycholic (URSO). The administration of Gris alone increased the activities of glutathione reductase (GRed), superoxide dismutase (SOD), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), and glutathione-S-transferase (GST), as well as total porphyrins, glutathione (GSH), and cytochrome P450 (CYP) levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris.

Dynamic mechanistic modeling of the multienzymatic one-pot reduction of dehydrocholic acid to 12-keto ursodeoxycholic acid with competing substrates and cofactors.

Ursodeoxycholic acid (UDCA) is a bile acid which is used as pharmaceutical for the treatment of several diseases, such as cholesterol gallstones, primary sclerosing cholangitis or primary biliary cirrhosis. A potential chemoenzymatic synthesis route of UDCA comprises the two-step reduction of dehydrocholic acid to 12-keto-ursodeoxycholic acid (12-keto-UDCA), which can be conducted in a multienzymatic one-pot process using 3α-hydroxysteroid dehydrogenase (3α-HSDH), 7ß-hydroxysteroid dehydrogenase (7ß-HSDH), and glucose dehydrogenase (GDH) with glucose as cosubstrate for the regeneration of cofactor. Here, we present a dynamic mechanistic model of this one-pot reduction which involves three enzymes, four different bile acids, and two different cofactors, each with different oxidation states. In addition, every enzyme faces two competing substrates, whereas each bile acid and cofactor is formed or converted by two different enzymes. First, the kinetic mechanisms of both HSDH were identified to follow an ordered bi-bi mechanism with EBQ-type uncompetitive substrate inhibition. Rate equations were then derived for this mechanism and for mechanisms describing competing substrates. After the estimation of the model parameters of each enzyme independently by progress curve analyses, the full process model of a simple batch-process was established by coupling rate equations and mass balances. Validation experiments of the one-pot multienzymatic batch process revealed high prediction accuracy of the process model and a model analysis offered important insight to the identification of optimum reaction conditions.

Multi-enzymatic one-pot reduction of dehydrocholic acid to 12-keto-ursodeoxycholic acid with whole-cell biocatalysts.

Ursodeoxycholic acid (UDCA) is a bile acid of industrial interest as it is used as an agent for the treatment of primary sclerosing cholangitis and the medicamentous, non-surgical dissolution of gallstones. Currently, it is prepared industrially from cholic acid following a seven-step chemical procedure with an overall yield of <30%. In this study, we investigated the key enzymatic steps in the chemo-enzymatic preparation of UDCA-the two-step reduction of dehydrocholic acid (DHCA) to 12-keto-ursodeoxycholic acid using a mutant of 7ß-hydroxysteroid dehydrogenase (7ß-HSDH) from Collinsella aerofaciens and 3α-hydroxysteroid dehydrogenase (3α-HSDH) from Comamonas testosteroni. Three different one-pot reaction approaches were investigated using whole-cell biocatalysts in simple batch processes. We applied one-biocatalyst systems, where 3α-HSDH, 7ß-HSDH, and either a mutant of formate dehydrogenase (FDH) from Mycobacterium vaccae N10 or a glucose dehydrogenase (GDH) from Bacillus subtilis were expressed in a Escherichia coli BL21(DE3) based host strain. We also investigated two-biocatalyst systems, where 3α-HSDH and 7ß-HSDH were expressed separately together with FDH enzymes for cofactor regeneration in two distinct E. coli hosts that were simultaneously applied in the one-pot reaction. The best result was achieved by the one-biocatalyst system with GDH for cofactor regeneration, which was able to completely convert 100 mM DHCA to >99.5 mM 12-keto-UDCA within 4.5 h in a simple batch process on a liter scale.

One-step synthesis of 12-ketoursodeoxycholic acid from dehydrocholic acid using a multienzymatic system.

12-ketoursodeoxycholic acid (12-keto-UDCA) is a key intermediate for the synthesis of ursodeoxycholic acid (UDCA), an important therapeutic agent for non-surgical treatment of human cholesterol gallstones and various liver diseases. The goal of this study is to develop a new enzymatic route for the synthesis 12-keto-UDCA based on a combination of NADPH-dependent 7ß-hydroxysteroid dehydrogenase (7ß-HSDH, EC 1.1.1.201) and NADH-dependent 3α-hydroxysteroid dehydrogenase (3α-HSDH, EC 1.1.1.50). In the presence of NADPH and NADH, the combination of these enzymes has the capacity to reduce the 3-carbonyl- and 7-carbonyl-groups of dehydrocholic acid (DHCA), forming 12-keto-UDCA in a single step. For cofactor regeneration, an engineered formate dehydrogenase, which is able to regenerate NADPH and NADH simultaneously, was used. All three enzymes were overexpressed in an engineered expression host Escherichia coli BL21(DE3)Δ7α-HSDH devoid of 7α-hydroxysteroid dehydrogenase, an enzyme indigenous to E. coli, in order to avoid formation of the undesired by-product 12-chenodeoxycholic acid in the reaction mixture. The stability of enzymes and reaction conditions such as pH value and substrate concentration were evaluated. No significant loss of activity was observed after 5 days under reaction condition. Under the optimal condition (10 mM of DHCA and pH 6), 99 % formation of 12-keto-UDCA with 91 % yield was observed.

Novel whole-cell biocatalysts with recombinant hydroxysteroid dehydrogenases for the asymmetric reduction of dehydrocholic acid.

Ursodeoxycholic acid is an important pharmaceutical so far chemically synthesized from cholic acid. Various biocatalytic alternatives have already been discussed with hydroxysteroid dehydrogenases (HSDH) playing a crucial role. Several whole-cell biocatalysts based on a 7α-HSDH-knockout strain of Escherichia coli overexpressing a recently identified 7ß-HSDH from Collinsella aerofaciens and a NAD(P)-bispecific formate dehydrogenase mutant from Mycobacterium vaccae for internal cofactor regeneration were designed and characterized. A strong pH dependence of the whole-cell bioreduction of dehydrocholic acid to 3,12-diketo-ursodeoxycholic acid was observed with the selected recombinant E. coli strain. In the optimal, slightly acidic pH range dehydrocholic acid is partly undissolved and forms a suspension in the aqueous solution. The batch process was optimized making use of a second-order polynomial to estimate conversion as function of initial pH, initial dehydrocholic acid concentration, and initial formate concentration. Complete conversion of 72 mM dehydrocholic acid was thus made possible at pH 6.4 in a whole-cell batch process within a process time of 1 h without cofactor addition. Finally, a NADH-dependent 3α-HSDH from Comamonas testosteroni was expressed additionally in the E. coli production strain overexpressing the 7ß-HSDH and the NAD(P)-bispecific formate dehydrogenase mutant. It was shown that this novel whole-cell biocatalyst was able to convert 50 mM dehydrocholic acid directly to 12-keto-ursodeoxycholic acid with the formation of only small amounts of intermediate products. This approach may be an efficient process alternative which avoids the costly chemical epimerization at C-7 in the production of ursodeoxycholic acid.

Biophysical investigations into the interactions of endotoxins with bile acids.

The interaction of selected endotoxin preparations (lipid A from Erwinia carotovora and LPS Re and Ra from Salmonella enterica sv. Minnesota strains R595 and R60, respectively) with selected bile acids was investigated biophysically. Endotoxin aggregates were analyzed for their gel-to-liquid crystalline phase behavior, the type of their aggregates, the conformation of particular functional groups, and their Zeta potential in the absence and presence of the bile acids by applying Fourier-transform infrared spectroscopy, differential scanning calorimetry, measurements of the electrophoretic mobility, and synchrotron radiation X-ray scattering. In addition, the ability of the endotoxins to induce cytokines in human mononuclear cells was tested in the absence and presence of varying concentrations of bile acids. The data show that the endotoxin:bile acid interaction is not governed by Coulomb forces, rather a hydrophobic interaction takes place. This leads to an enhanced formation of the inherent cubic aggregate structures of the endotoxins, concomitant with a slight disaggregation, as evidenced by freeze-fracture electron microscopy. Parallel to this, the addition of bile acids increased the bioactivity of lipid A and, to a lower degree, also that of the tested rough mutant LPS at lower concentrations of the endotoxin preparation, a finding similar as reported for the interaction of other agents such as hemoglobin. These data imply that there are general mechanisms that govern the expression of biological activities of endotoxins.

Preparation and characterization of uniform drug particles: dehydrocholic acid.

Two methods for the preparation of uniform dispersions of dehydrocholic acid of different morphologies are described. In the first case, the drug was dissolved in acetone and then re-precipitated by adding a non-solvent (either water or an aqueous stabilizer solution), which yielded rod-like particles. In the second procedure, spheres, consisting of small elongated subunits, were obtained by acidification of basic aqueous solutions of the drug. The resulting particles were characterized in terms of their structure and surface charge characteristics.

Ursodeoxycholic acid is conjugated with taurine to promote secretin-stimulated biliary hydrocholeresis in the normal rat.

BACKGROUND & AIMS: Secretin induces bicarbonate-rich hydrocholeresis in healthy individuals, but not in untreated patients with primary biliary cirrhosis (PBC). Ursodeoxycholic acid (UDCA)--the first choice treatment for PBC--restores the secretin response. Compared with humans, secretin has poor effect in experimental normal-rat models with biliary drainage, although it may elicit hydrocholeresis when the bile-acid pool is maintained. In view of the benefits of UDCA in PBC, we used normal-rat models to unravel the acute contribution of UDCA (and/or taurine-conjugated TUDCA) for eliciting the biliary secretin response. METHODS: Intravascular and/or intrabiliary administration of agonists and inhibitors was performed in normal rats with biliary monitoring. Secretin/bile-acid interplay was analyzed in 3D cultured rat cholangiocytes that formed expansive cystic structures with intralumenal hydroionic secretion. RESULTS: In vivo, secretin stimulates hydrocholeresis upon UDCA/TUDCA infusion, but does not modify the intrinsic hypercholeretic effect of dehydrocholic acid (DHCA). The former effect is dependent on microtubule polymerization, and involves PKCα, PI3K and MEK pathways, as shown by colchicine (i.p.) and retrograde biliary inhibitors. In vitro, while secretin alone accelerates the spontaneous expansion of 3D-cystic structures, this effect is enhanced in the presence of TUDCA, but not UDCA or DHCA. Experiments with inhibitors and Ca(2+)-chelator confirmed that the synergistic effect of secretin plus TUDCA involves microtubules, intracellular Ca(2+), PKCα, PI3K, PKA and MEK pathways. Gene silencing also demonstrated the involvement of the bicarbonate extruder Ae2. CONCLUSIONS: UDCA is conjugated in order to promote secretin-stimulated hydrocholeresis in rats through Ae2, microtubules, intracellular Ca(2+), PKCα, PI3K, PKA, and MEK.

Improvement of oxaprozin solubility and permeability by the combined use of cyclodextrin, chitosan, and bile components.

The effect of the combined use of randomly methylated ß-cyclodextrin (RAMEB), chitosan (CS), and bile components (dehydrocholic (DHCA) or ursodeoxycholic (UDCA) acids and their sodium salts) on solubility and permeability through Caco-2 cells of oxaprozin (a very poorly water-soluble non-steroidal anti-inflammatory drug) has been investigated. Addition of CS, bile acids, and their sodium salts increased the RAMEB solubilizing power of 4, 2, and 5 times, respectively. Drug-RAMEB-CS co-ground systems showed very higher dissolution rate than corresponding drug-RAMEB systems. Addition of bile components further improved drug dissolution rate. The CS presence enabled a significant increase in drug permeability through Caco-2 cells with respect to drug-RAMEB systems. Moreover, CS and NaDHC showed a synergistic enhancer effect, enabling a 1.4-fold permeability increase in comparison with systems without bile salt. However, unexpectedly, no significant differences were found between physical mixtures and co-ground products, indicating that drug permeation improvement was due to the intrinsic enhancer effect of the carriers and not to drug-carrier interactions brought about by co-grinding, as instead found in dissolution rate studies. The combined use of RAMEB, CS, and NaDHC could be exploited to develop effective oral dosage forms of oxaprozin, with increased drug solubility and permeability, and then improved bioavailability.

Thermodynamic and elastic fluctuation analysis of Langmuir mixed monolayers composed by dehydrocholic acid (HDHC) and didodecyldimethylammonium bromide (DDAB).

The physicochemical and elastic properties of Langmuir mixed monolayers composed by dehydrocholic acid (HDHC) and didodecyldimethylammonium bromide (DDAB) were evaluated. The experiments were performed with a constant surface pressure penetration Langmuir balance based on Axisymmetric Drop Shape Analysis (ADSA). The behavior of such amphiphiles in monolayer was clearly non-ideal and would be seriously influenced by the amount of HDHC molecules present. The presence of bile acid type molecules caused the monolayer be more condensed (A(c) diminution) and the intermolecular attractive interactions be stronger (high epsilon(0) values). This fact would be related to H-bond formation between water and carboxilate and carbonile groups in the cholesteric ring and agreed with the existence of laterally structured microdomains at the monolayer (determined by the analysis of the first virial coefficient, b(0)<1, of the state equation). The miscibility of both surfactants in the monolayer, their high bulk hydrophobicity (pi(c)>35 mJ m(-2)) just with the obtained negative values of the free energy of mixing Delta G(mix), and the excess second virial coefficient (b(1))(E) obtained allows us to infer that net attractive interaction existed between HDHC and DDAB molecules at the monolayer and that mixed systems would be able to be used in the formulation of supramolecular assemblies.

Surgical outcome in relation to duct size at the porta hepatis and the use of cholagogues in patients with biliary atresia.

BACKGROUND: Small ductules communicating with the bile ducts have been described at the porta hepatis in extrahepatic biliary atresia (EHBA) and these form the basis for hepatic portoenterostomy. The use of cholagogues like dehydrocholic acid (DHC) and ursodeoxycholic acid (UDCA) to enhance bile flow postoperatively has been reported. AIMS: This communication describes our experience with the use of cholagogues following surgery in EHBA and attempts to correlate the outcomes with the diameter of the ductules. MATERIAL AND METHODS: Fifty five EHBA patients treated by the Kasai procedure form the basis of this study; 35 patients treated during 1979-1986 and administered DHC (3-5 mg/kg) postoperatively and 20 patients treated during 1999-2002 and administered UDCA (15 mg/kg) postoperatively. The diameter of ductules was measured using an optical micrometer on 5 microm serial sections; the ducts were classified as type I (no demonstrable ducts, n = 14), type II (< 50 microm, n=22) and type III (> 50 microm, n = 19). The clinical outcome was categorized as 1 (jaundice free survival at 5 years follow-up, n = 7), 2 (initial good response but deteriorated after one year, n = 27) and 3 (expired within one year following surgery, n = 21). The response to surgery was monitored using biochemical liver function tests (LFT), hepatobiliary scintigraphy (HIDA scan) and occurrence of cholangitis. RESULTS: Age did not affect the size of ducts in both DHC and UDCA groups but patients in the DHC group were older than those treated with UDCA (mean age DHC: 105.22 +/- 33.53 days, UDCA: 74.68 +/- 23.73 days; p = 0.009). There was no statistically significant difference between duct size and postoperative LFT in both groups (DHC p = 0.1, UDCA p = 0.5). Bile excretion on HIDA scan was significantly better with larger ducts (DHC p = 0.003, UDCA p = 0.025); overall UDCA showed significantly better bile excretion (p = 0.003) but this was not reflected in the surgical outcome. There was no significant difference in the surgical outcome of those treated with DHC or UDCA but a significantly higher incidence of cholangitis was seen with smaller ducts in the UDCA group (p = 0.02). CONCLUSIONS: There was no correlation between duct diameter and postoperative LFT but type III ducts were associated with better bile flow on HIDA scan. Cholangitis was seen more often with type I and II ducts in both DHC and UDCA groups. UDCA administration seemed to be beneficial in patients with type III ducts in increasing bile flow and reducing cholangitis.

Roles of the outer membrane protein AsmA of Salmonella enterica in the control of marRAB expression and invasion of epithelial cells.

A genetic screen for suppressors of bile sensitivity in DNA adenine methylase (dam) mutants of Salmonella enterica serovar Typhimurium yielded insertions in an uncharacterized locus homologous to the Escherichia coli asmA gene. Disruption of asmA suppressed bile sensitivity also in phoP and wec mutants of S. enterica and increased the MIC of sodium deoxycholate for the parental strain ATCC 14028. Increased levels of marA mRNA were found in asmA, asmA dam, asmA phoP, and asmA wec strains of S. enterica, suggesting that lack of AsmA activates expression of the marRAB operon. Hence, asmA mutations may enhance bile resistance by inducing gene expression changes in the marRAB-controlled Mar regulon. In silico analysis of AsmA structure predicted the existence of one transmembrane domain. Biochemical analysis of subcellular fractions revealed that the asmA gene of S. enterica encodes a protein of approximately 70 kDa located in the outer membrane. Because AsmA is unrelated to known transport and/or efflux systems, we propose that activation of marRAB in asmA mutants may be a consequence of envelope reorganization. Competitive infection of BALB/c mice with asmA(+) and asmA isogenic strains indicated that lack of AsmA attenuates Salmonella virulence by the oral route but not by the intraperitoneal route. Furthermore, asmA mutants showed a reduced ability to invade epithelial cells in vitro.

A new approach for diagnosis of hepatolithiasis: magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of hepatolithiasis.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of hepatolithiasis. METHODOLOGY: Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of hepatolithiasis in 8 of 9 cases (88.9%). CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the hepatolithiasis on MRCP images.

Magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of biliary disease.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of the biliary tree. METHODOLOGY: Our study population comprised 14 patients. Magnetic resonance cholangiopancreatography was acquired before and after the administration of DHCA. Two different MRCP snap shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. Volume rendering was prepared based on the source images, and the pixel size was visually adjusted to the biliary area of MRCP to measure the biliary tree volume. RESULTS: DHCA increased the bile duct volume in 13 of the 14 patients. It provided a better visualization of the biliary tree in 11 patients. The three patients without improvement in visualization included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 2 patients with cholecystectomy who had the bile ducts filled with bile by the time of the administration. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the biliary tree on MRCP images.

Magnetic resonance cholangiopancreatography: potential usefulness of dehydrocholic acid (DHCA) administration in the evaluation of anastomotic site.

BACKGROUND/AIMS: The aim of this study was to investigate whether exogenous dehydrocholic acid (DHCA) was useful to enhance the delineation of anastomotic site. METHODOLOGY: DHCA is a cholagogue which produces an immediate effect by acting directly on liver cells. Its choleretic effect is strong, appearing 1 to 3 minutes after intravenous injection, reaching the maximum level in 20 to 30 minutes. Our study population comprised 9 patients. Magnetic resonance cholangiopancreatography (MRCP) was acquired before and after the administration of DHCA. Two different MRCP snap-shot techniques were applied: thick-slab two-dimensional (2D) (coronal) single-shot turbo spin echo T2-weighted sequences and multisection thin-slab, 2D (coronal) single shot turbo spin echo T2-weighted sequences with three-dimensional (3D) maximum intensity projection (MIP) post processing. RESULTS: DHCA provided a better visualization of the anastomotic site in 7 patients (77.8%). The two patients without improvement in visualization of anastomotic site included 1 patient with liver cirrhosis secondary to portoenterostomy for congenital biliary dilatation and 1 patient, who was not eligible for the evaluation because of motion artifact caused by the difficulty of breath holding motion artifact. CONCLUSIONS: It was suggested that administration of DHCA could enhance the delineation of the anastomotic site on MRCP images.