Therapeutic Effects Of Ursodeoxycholic Acid Research Articles

Drug regulation of microRNA

The scientific review provides the mechanisms of drug regulation of microRNA in the human body. To write the article, information was searched using Scopus, Web of Science, MEDLINE, PubMed, Google Scholar, Embase, Global Health, The Cochrane Library databases. To restore the reduced functional activity of microRNAs, replacement therapy is used, with modified synthetic analogs of endogenous microRNAs, and drugs that enhance the production of the body’s own microRNAs. The authors state that numerous studies have confirmed the effectiveness of miRNA replacement therapy. It is known that there are several groups of drugs among miRNA inhibitors: anti-miRNA oligonucleotides, miRNA traps, miRNA mimics that prevent miRNA binding; peptide nucleic acids, small-molecule inhibitors. The authors suggest that the expression of drug-metabolizing enzymes is controlled by nuclear receptors and transcription factors, epigenetic regulation such as DNA methylation and histone acetylation, and post-translational modification. It is emphasized that ursodeoxycholic acid modulates the expression of some miRNAs. It is known that probiotic bacteria can modulate the expression level of miRNA genes. The use of probiotics is accompanied by a change in the expression of nume­rous genes of the body involved in the regulation of the inflammatory response, allergic reactions, metabolism and other biological processes. Thus, modern science is intensively studying the potential of using drugs that restore miRNA content or inhibit miRNA acti­vity for the therapy of miRNA-dependent conditions. The results of scientific research confirmed the therapeutic effect of ursodeoxycholic acid and probiotic preparations due to the effect on the acti­vity of miRNA generation in hepatobiliary diseases. Therefore, the introduction into clinical practice of drugs than can modulate the content and expression of specific miRNAs will certainly open new perspectives in the treatment of patients with hepatobiliary diseases.

Potential therapeutic benefit of ursodeoxycholic acid in the management of non hepato-biliary upper gastrointestinal disorders.

To examine the potential therapeutic effects of ursodeoxycholic acid (UDCA) on diseases of the esophagus, stomach, and duodenum. A search was conducted using EBSCO, Medline, PubMed, Google Scholar and Web of Science as well as international guidelines using MESH terms for treatment of UDCA for diseases of the upper gastrointestinal disorders in adult humans without regard to publication language or date restrictions. A total of 256 articles and 22 guidelines were initially identified, and 221 were excluded. Final revision of 13 articles and 22 guidelines confirmed that UDCA is found to have a cytoprotective role in Barret's esophagus within esophageal disorders, improves abdominal pain in functional dyspepsia, and does not alter Helicobacter pylori colonization or inflammation. Conflicting results are noted regarding the role of UDCA in the duodenum as chemopreventive treatment for familial adenomatous polyposis, with polyps regressing and their growth characteristics improving with low doses (10-25mg/kg/day). On the contrary, no positive effect was noted upon the combination with Celecoxib and with doses of 1000-2000mg or 20-30mg/kg/d. Gastrointestinal side effects were predominantly reported. No side effects necessitated hospitalization or ICU admission. Ursodeoxycholic acid has a limited therapeutic role in functional dyspepsia. There is promising evidence that it may serve as a chemopreventive for Familial adenomatous polyposis and Barret's esophagus, although further research is needed to confirm these findings.PROSPERO No.: CRD 42021267689.

Potential Therapeutic Effects of Ursodeoxycholic Acid in Comparison to Ramipril in a Rat model of Diabetic Nephropathy

Abstract Background & Aim Diabetic nephrectomy (DN) is a chronic progressive disorder that complicates long standing diabetes. Albuminuria is a prominent clinical feature of DN. Ursodeoxycholic acid (UDCA) is a physiologic hydrodrophillic bile acid that is therapeutically used in the treatment of primary biliary cirrhosis. It is known to alleviate endoplasmic reticulum (ER) stress in podocytes. In comparison to Ramipril as a standard ACEI therapy of DN, the present study was designed to investigate the effect of UDCA treatment on DN in association with renal biomarkers changes. Method Four groups of male Wister rats (6 per group) were designed; Normal control group, DN untreated group (High fat diet + STZ injection of 45 mg/kg + uninephrectomy), DN/Ramipril group; (1 mg/kg/d orally for 12 weeks) and DN/UDCA group (40 mg/kg/d orally for 12 weeks). Results DN rats treated with UDCA for 12 weeks exhibited significant decrease in ER stress marker, ATF6 with mean percentage value of 73.8% and improvement of podocyte structural deformities that is accompanied by a significant reduction in albuminuria by mean percentage value of 43.8% comparatively to Ramipril that caused reduction in ATF6 level with mean percentage value of 65.5% and reduction in albuminuria by mean percentage value of 50.2%. The remarkable improvement in metabolic profile and the neutral effect on blood pressure in UDCA treated group could explain the renoprotection at histopathological basis rather than the proved hemodynamic effect of ramipril. Conclusion Participation of ER stressmediated apoptosis in the pathophysiology of diabetic nephropathy make the UDCA a potential therapeutic option or add-on therapy due to its anti-apoptotic property apart from classic metabolic and hemodynamic aspects.

Ursodeoxycholic acid and its unexpected application areas

Introduction. Ursodeoxycholic acid (UDCA) came into modern medicine in the 1970s as a potential solvent for small gallstones. But as early as the 1980s, there were clinical studies to improve biochemical indices when using UDCA in other liver diseases. These studies initiated a worldwide active study of the clinical possibilities and various therapeutic effects of UDCA in various diseases, including those beyond the liver. Today, worldwide, UDCA drugs are the lifelong basis for the treatment of primary sclerosing cholangitis (PSC). It is indicated for all types of hepatitis: infectious, toxic, drug-induced, autoimmune and others. It can be stated that the history of study and introduction of UDCA drugs in medicine is the history of the expansion of its application areas, which continues to this day. The purpose of the review is to present the results of the use of UDCA drugs outside the traditional circle of cholestatic liver diseases, the causes and possibilities of their use in other areas of medicine. Main principles. It has been shown that UDCA, originally designed for the treatment of cholestatic liver diseases, along with the known antioxidant, antifibrotic and immunomodulatory effects has a proven fundamental apoptosis regulatory effect. This allows it to have as a possible therapeutic target a whole range of extrahepatic diseases, such as gastrointestinal lesions (IBD, clostridi-osis, radiation and medical intestinal lesions, etc.), diseases of the cardiovascular system, neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, ALS), prion diseases (Kuru, Creutzfeldt-Jakob disease) and a number of others. Conclusion. According to modern views, UDCA can be considered as a unique drug of universal cytoprotective action, the expansion of its therapeutic possibilities is promising and is subject to further multilateral study.

Therapeutic Effects of Ursodeoxycholic Acid in Neonatal Indirect Hyperbilirubinemia; a Randomized Double-Blind Clinical Trial

Background: Ursodeoxycholic acid (UDCA) is a safe drug used in the treatment of cholestatic liver disorders in children. The aim of this study was to investigate the synergistic effect of UDCA in combination with phototherapy in treating indirect neonatal hyperbilirubinemia.
 Methods: Present double-blinded, randomized clinical trial was conducted among neonates with jaundice who were under treatment with phototherapy in the neonatal ward affiliated with the Zabol University of Medical Sciences in 2017. The patients (200 neonates) were randomly divided into intervention (phototherapy+ UDCA) and control (phototherapy alone) groups. The intervention group received 15 mg/kg UDCA daily.
 Results: Total bilirubin levels at birth, 24, 48, and 72 hours after therapy were 16.89± 2.49, 14.28± 2.05, 11.62± 2.46, and 10.26± 1.92 mg/dl in controls and 15.79± 2.18, 12.77± 1.86, 10.08± 1.66, and 8.94± 1.38 mg/dl in intervention group respectively (P< 0.001). The ratio of neonates with total bilirubin< 10 mg/dl were 28% and 55% after 48 hours, and 64% and 90% after 72 hours of therapy initiation in phototherapy alone and phototherapy+ UDCA groups respectively (P< 0.001). The mean reduction of direct bilirubin was not significantly different between the groups.
 Conclusion: UDCA was effective in accelerating reduction of total bilirubin level in neonates with unconjugated hyperbilirubinemia under phototherapy but had no effect on direct bilirubin levels.

Anti-neuroinflammatory gold nanocomplex loading ursodeoxycholic acid following spinal cord injury

Spinal cord injury (SCI) causes permanent nerve damage by disturbing axon regeneration from pro-inflammations and still remains a serious worldwide problem. Ursodeoxycholic acid (UDCA) has been reported that it can serve as an anti-neuroinflammatory drug such as Methylprednisolone (MP). However, the therapeutic effect of UDCA is limited due to its hydrophobic property. In this study, we aimed to investigate the anti-neuroinflammatory effects of gold nanoparticles (GNPs) loading UDCA (GNP-UDCA complex) following SCI. For this, we conjugated with β-cyclodextrin (β-CD) on the GNP’s surface and included UDCA in β-CD by sonicating. We confirmed that the GNP-UDCA complex successfully synthesized. A mechanical SCI was imposed on rats and we injected GNP-UDCA complex three times after injury. After SCI, motor function and the lesions were significantly improved in the GNP-UDCA complex group than those in MP group and UDCA group. This complex significantly decreased pro-inflammatory cytokines and increased anti-inflammatory cytokines in terms of mRNA and protein levels than MP and UDCA. In addition, GNP-UDCA complex significantly suppressed the phosphorylation of extracellular signal-regulated kinase (p-ERK) and c-Jun N-terminal kinase (p-JNK) in the mitogen-activated protein kinase (MAPK) pathway than MP and UDCA. Finally, the complex significantly exhibited the expression of inducible nitric oxide synthase (iNOS). It also induced the expression of arginase-1 (Arg-1), anti-inflammatory marker, at the injured sites more than that in the saline group. In conclusion, this study demonstrates the anti-neuroinflammatory effects of GNP-UDCA complex in SCI and suggests that the GNP-UDCA complex can be an alternative drug system for SCI cases.

Ursodeoxycholic acid in biliary pathology: current concepts

Ursodeoxycholic acid (UDCA) is a drug commonly used in clinical practice. This article is devoted to a review of research of the possibility of using UDCA for biliary system diseases. Prevention of the formation and dissolution of gallstones is one of the first and main indications for administration of UDCA. This was the beginning of the era of this amazing pleiotropic molecule in the 80s of the last century. UDCA preparations are based on chemical synthesis, but they have a natural origin and have a complex effect at the level of the organism as a whole. The therapeutic effect of UDCA is directed at once to several pathogenetic links that normalize human metabolism. This allows to avoid polypragmasy of medical prescriptions and is important not only in terms of the efficacy and safety of the treatment, but also in optimizing the economic costs of purchasing medicines for patients with comorbid pathology, often the elderly. The article briefly presents epidemiology of gallstone disease, clinical manifestations, features of changes in the composition of bile during development of cholelithiasis. The characteristic of the UDCA molecule by the mechanism of action is presented. The advantages of UDCA compared with medicinal herbs and herb-based preparations; in particular, safety of use and the pleiotropic nature of the UDCA molecule, are discussed, as well as its role in normalization of metabolic processes in the human body, especially lipid metabolism. Dysfunctional disorders of the biliary tract, biliary sludge and cholelithiasis are considered in detail. Attention is paid to formation of gallstones against the background of genetic mutations (mutations in the gene encoding the phosphatidylcholine flopase ABCB4; mutations of the UGT1A1 gene responsible for development of the Gilbert’s disease or Gilbert’s syndrome). The recommended doses and mode of administration of UDCA in these indications are indicated according to modern clinical concepts. The accumulated successful experience in their conservative treatment with the help of UDCA instills optimism in achieving positive results in the form of normalization of biliary motility, elimination of biliary insufficiency, elimination of biliary sludge, primary prevention and treatment of gallstone disease.

Activation of PPARγ inhibits hepatic cholestasis with involvement of Nogo‐B expression

Hepatic cholestasis can develop to fibrosis, cirrhosis and liver failure. Currently, the therapeutic effect of ursodeoxycholic acid (UDCA) on primary biliary cirrhosis (PBC) is limited to early stages of the disease. Recently, obeticholic acid (OCA) has been approved by FDA for the treatment of PBC. However, the safety, efficacy and tolerance of OCA may need further investigation in clinics. Herein, we report the effect of peroxisome proliferator activated receptor γ (PPARγ), a ligand‐activated transcription factor, on hepatic cholestasis. Pre‐treatment of mice with a PPARγ ligand, rosiglitazone, substantially inhibited α‐naphthylisothiocyanate (ANIT)‐induced hepatic cholestasis in a PPARγ expression‐dependent manner. Rosiglitazone substantially reduced ANIT‐induced hepatic necrosis, restored muddy and dark colored bile and serum to normal. It also ameliorated serum biochemical parameters including ALT, AST, ALP, γ‐GT, total bilirubin and lipid profiles. In both mouse liver and HepG2 cells, activation of PPARγ induced expression of bile synthesis and secretion genes (CYP7A1, ABCB4, BSEP, ABCG5 and FXR) and Nogo‐B suggesting PPARγ enhances bile homeostasis and functions which might be involved with Nogo‐B expression. Surprisingly, we observed that deficiency of Nogo‐B expression in HepG2 cells greatly boosted expression of CYP7A1, ABCB4, ABCG5 and FXR while abolished PPARγ‐induced expression of these genes indicating the dual regulatory role of Nogo‐B in bile synthesis/secretion. In vivo, deficiency of Nogo‐B expression also increased expression of hepatic bile synthesis/secretion genes, and protected mice against ANIT‐induced hepatic cholestasis. Taken together, we identified that Nogo‐B is a target of PPARγ which might be involved in PPARγ‐inhibited cholestasis by its dual regulatory functions.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Clinical usefulness of ursodeoxycholic acid for Japanese patients with autoimmune hepatitis.

AIMTo evaluate the therapeutic effects of ursodeoxycholic acid (UDCA) on autoimmune hepatitis (AIH).METHODSA total 136 patients who were diagnosed with AIH were included in our study. All of the patients underwent a liver biopsy, and had at least a probable diagnosis on the basis of either the revised scoring system or the simplified scores. Initial treatment included UDCA monotherapy (Group U, n = 48) and prednisolone (PSL) monotherapy (Group P, n = 88). Group U was further classified into two subgroups according to the effect of UDCA: Patients who had achieved remission induction with UDCA monotherapy and showed no sign of relapse (Subgroup U1, n = 34) and patients who additionally received PSL during follow-up (Subgroup U2, n = 14). We compared the clinical and histological findings between each groups, and investigated factors contributing to the response to UDCA monotherapy.RESULTSIn Group U, 34 patients (71%) achieved and maintained remission over 49 (range: 8-90) mo (Subgroup U1) and 14 patients (29%) additionally received PSL (Subgroup U2) during follow-up. Two patients in Subgroup U2 achieved remission induction once but additionally required PSL administration because of relapse (15 and 35 mo after the start of treatment). The remaining 12 patients in Subgroup U2 failed to achieve remission induction during follow-up, and PSL was added during 7 (range: 2-18) mo. Compared with Subgroup U2, Subgroup U1 had significantly lower alanine aminotransferase (ALT) levels at onset (124 IU/L vs 262 IU/L, P = 0.023) and a significantly higher proportion of patients with mild inflammation (A1) on histological examination (70.6% vs 35.7%, P = 0.025). When multivariate analysis was performed to identify factors contributing to the response to UDCA monotherapy, only a serum ALT level of 200 IU/L or lower was found to be associated with a significant difference (P = 0.013).CONCLUSIONTo prevent adverse events related to corticosteroids, UDCA monotherapy for AIH needs to be considered in patients with a serum ALT level of 200 IU/L or lower.

Beneficial effects of combined ursodeoxycholic acid and angiotensin-II type 1 receptor blocker on hepatic fibrogenesis in a rat model of nonalcoholic steatohepatitis.

Ursodeoxycholic acid (UDCA) is considered to be effective in the treatment of nonalcoholic steatohepatitis (NASH), particularly in combination with other pharmacological agents. UDCA reportedly counteracts the effects of endotoxemia. Previously, we demonstrated attenuated hepatic fibrogenesis and suppression of activated hepatic stellate cells (Ac-HSC) with an angiotensin-II (AT-II) type 1 receptor blocker (ARB). Here we evaluated the simultaneous effect of both agents on hepatic fibrogenesis in a rat model of NASH. Fischer 344 rats were fed a choline-deficient L-amino-acid-defined (CDAA) diet for 8weeks. The therapeutic effect of UDCA and ARB was evaluated along with hepatic fibrogenesis, lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4) regulatory cascade, and intestinal barrier function. The direct inhibitory effect of both UDCA and ARB on Ac-HSC was assessed in vitro. Both UDCA and ARB had a potent inhibitory effect on hepatic fibrogenesis with suppression of the HSC activation and hepatic expression of transforming growth factor (TGF)-β1 and TLR4. UDCA decreased intestinal permeability by ameliorating zonula occuludens-1 (ZO-1) disruption induced by the CDAA diet. ARB was found to directly suppress regulation of Ac-HSC. UDCA and ARB have a synergistic repressive effect on hepatic fibrogenesis by counteracting endotoxemia induced by intestinal barrier dysfunction and suppressing the activation of Ac-HSC. Because both agents are currently used in clinical practice, combined UDCA and ARB may represent a promising novel therapeutic approach for NASH.

Serum vitamin D level is associated with disease severity and response to ursodeoxycholic acid in primary biliary cirrhosis.

Serum vitamin D levels are associated with bone complications in patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a nonskeletal role of vitamin D in various autoimmune and liver diseases. To investigate the clinical relevance of vitamin D levels in PBC, especially their association with the therapeutic effects of ursodeoxycholic acid (UDCA). Consecutive PBC patients were retrospectively reviewed. 25-hydroxyvitamin D [25(OH)D] levels were determined in frozen serum samples collected before initiation of UDCA treatment. Response to UDCA was evaluated by Paris-I and Barcelona criteria. Logistic regressions were performed to identify the treatment response-associated parameters. Among 98 patients, the mean serum 25(OH)D concentration was 17.9 ± 7.6 ng/mL. 25(OH)D levels decreased with increasing histological stage (P = 0.029) and were negatively correlated with bilirubin and alkaline phosphatase levels. After 1 year of UDCA therapy, 31 patients failed to achieve complete response according to Paris-I criteria. The baseline 25(OH)D level was significantly lower in nonresponders (14.8 ± 6.4 vs. 19.3 ± 7.6 ng/mL, P = 0.005). Vitamin D deficiency at baseline was associated with an increased risk of incomplete response independent of advanced stages (OR = 3.93, 95% CI = 1.02-15.19, P = 0.047). Similar results were obtained when biochemical response was evaluated by Barcelona criteria. Furthermore, 25(OH)D levels were lower in patients who subsequently suffered death or liver transplantation (12.1 ± 4.6 vs. 18.4 ± 7.6 ng/mL, P = 0.023). 25(OH)D level is associated with biochemical and histological features in PBC. Pre-treatment vitamin D status is independently related to subsequent response to UDCA. Our results suggest that vitamin D status may have important clinical significance in PBC.

Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid

Bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC gene family of unknown function. Rat BASIC (rBASIC) is inactive at rest. We have recently shown that cholangiocytes, the epithelial cells lining the bile ducts, are the main site of BASIC expression in the liver and identified bile acids, in particular hyo- and chenodeoxycholic acid, as agonists of rBASIC. Moreover, it seems that extracellular divalent cations stabilize the resting state of rBASIC, because removal of extracellular divalent cations opens the channel. In this addendum, we demonstrate that removal of extracellular divalent cations potentiates the activation of rBASIC by bile acids, suggesting an allosteric mechanism. Furthermore, we show that rBASIC is strongly activated by the anticholestatic bile acid ursodeoxycholic acid (UDCA), suggesting that BASIC might mediate part of the therapeutic effects of UDCA.

Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study

The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13-15 mg·kg(-1)·day(-1)) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1-2 but still progressed in patients at stages 3-4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3-4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis

Microlithiasis has been identified as a cause of idiopathic acute pancreatitis in patients with an intact gallbladder. Microlithiasis has also been identified in the bile of some patients who have undergone cholecystectomy. However, it is unknown whether bile microlithiasis causes postcholecystectomy pain. To identify bile microlithiasis in patients with postcholecystectomy pain and to investigate the therapeutic effect of ursodeoxycholic acid (urso) on such patients with microlithiasis in the bile. Prospective randomized trial. Tertiary medical center. Patients with postcholecystectomy pain and bile crystals. Urso treatment. The severity and frequency of right upper-quadrant abdominal pain were compared with and without urso treatment, and before and after urso treatment. A total of 118 patients with postcholecystectomy pain were screened for the study. Twelve patients (10%) were identified with bile crystals. In the first phase, 6 of these patients received urso treatment, whereas the other 6 patients did not receive urso treatment. In the second phase, the latter 6 patients were given the urso treatment. After using urso for a few months, their biliary-type abdominal pain significantly improved or resolved. In the control group, there was no improvement in symptoms. There was a significant difference between the 2 groups (P = .01). Single-center, small number of patients. This study provided evidence that supports the hypothesis that bile microlithiasis is indeed a cause for postcholecystectomy pain. Patients with such postcholecystectomy pain may benefit from a microscopic examination of bile for crystals or microlithiasis, and urso treatment if bile crystals are identified.

Effects of Ursodeoxycholic and Cholic Acid Feeding on Hepatocellular Transporter Expression in Mouse Liver

Background & Aims: Cholestasis is associated with retention of potentially toxic bile acids and alterations in hepatocellular transporter expression. Conversely, nontoxic ursodeoxycholic acid (UDCA) stimulates bile secretion and counteracts cholestasis. This study aimed to determine the effects of UDCA and cholic acid (CA) on the expression of hepatocellular transporters for bile acids (Ntcp, Bsep), organic anions (Oatp1, Mrp2), organic cations (Mdr1a/b), and phospholipids (Mdr2) in mouse liver. Methods: Bile flow/composition was analyzed in UDCA- or CA-fed mice. Transporter expression was studied by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence microscopy. Results: UDCA had no effect on basolateral Ntcp and down-regulated Oatp1, whereas canalicular Bsep and Mrp2 were up-regulated. CA down-regulated basolateral Ntcp and Oatp1, whereas canalicular Bsep, Mrp2, and Mdr1a/b were up-regulated. Neither UDCA nor CA affected Mdr2 expression. Both UDCA and CA stimulated biliary bile acid and glutathione excretion, although only CA increased phospholipid and cholesterol excretion. Conclusions: Down-regulation of basolateral and up-regulation of canalicular transporters in response to CA may represent a defense mechanism, in an attempt to prevent hepatocellular accumulation of potentially toxic bile acids. The therapeutic effects of UDCA may be caused in part by stimulation of canalicular transporter expression in the absence of hepatocellular toxicity.

Cholestatic diseases of the liver

With respect to primary biliary cirrhosis (PBC), much progress has been made in the past few years in the identification of the immunodominant autoepitopes and HLA molecules involved in the immune response to mitochondrial antigens. An immunodominant region of the inner lipoyl domain could be identified by analyzing either T-or B-cell clones specific for the pyruvate dehydrogenase complex (PDC)-E2-subunit. Molecular mimicry continues to be discussed as a possible mechanism for the induction of autoreactive T and B cells, and cross-reactivity with exogenous PDC-E2 could be demonstrated. Abnormal expression of PDC-E2 on the apical region of biliary epithelial cells has also been observed in the affected liver. For primary sclerosing cholangitis (PSC), an immune-mediated etiology is also believed to account for bile duct lesions as evidenced by the close association with certain HLA haplotypes and the high association with antineutrophil cytoplasmic antibodies. However, evidence for organ specificity is still lacking on the humoral and cellular level. The increased risk for the development of bile duct carcinoma in PSC could again be demonstrated. The mode of action and therapeutic effect of ursodeoxycholic acid has been intensively evaluated in both diseases and has been shown to be of benefit especially in early stages. Cholestatic liver diseases after intake of diclofenac particularly have been studied, and hypersensitivity reactions seem to play a major role in the pathogenesis of these drug-induced liver disorders.

Increased serum IgM class anti-lipid a antibody and therapeutic effect of ursodeoxycholic acid in primary biliary cirrhosis

Increased serum IgM class anti-lipid a antibody and therapeutic effect of ursodeoxycholic acid in primary biliary cirrhosis

Pharmacological Aspects and Therapeutic Effects of Ursodeoxycholic Acid

Pharmacological Aspects and Therapeutic Effects of Ursodeoxycholic Acid