Adherence to guideline recommendations for Barrett's esophagus (BE) surveillance endoscopies: Effects of dedicated BE endoscopy lists.

Background and study aims For non-dysplastic Barrett's Esophagus (BE) patients, guidelines recommend endoscopic surveillance every 3 to 5 years with four-quadrant random biopsies every 2 cm of BE length. Adherence to these guidelines is low in clinical practice. Pooling BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists could possibly enhance guideline adherence, detection of visible lesions, and dysplasia detection rates (DDRs). Patients and methods Data were used from the ACID-study (Netherlands Trial Registry NL8214), a prospective trial of BE surveillance in the Netherlands. BE patients with known or previously treated dysplasia were excluded. Guideline adherence, detection of visible lesions, and DDRs were compared for patients on dedicated and general endoscopy lists. Results A total of 1,244 patients were included, 318 on dedicated lists and 926 on general lists. Endoscopies on dedicated lists showed significantly higher adherence to the random biopsy protocol (85% vs. 66%, P <0.01) and recommended surveillance intervals (60% vs. 47%, P <0.01) compared to general lists. Detection of visible lesions (8.8% vs. 8.1%, P =0.79) and DDRs were not significantly different (6.9% and 6.6%, P =0.94). None (0.0%) of the patients scheduled on dedicated lists and 10 (1.1%) on general lists were diagnosed with esophageal adenocarcinoma ( P =0.07). In multivariable analysis, dedicated lists were significantly associated with biopsy protocol adherence and adherence to surveillance interval recommendations with odds ratios of 4.45 (95% confidence interval [CI] 2.07-9.57) and 1.64 (95% CI 1.03-2.61), respectively. Conclusions Dedicated endoscopy lists are associated with better adherence to the random biopsy protocol and surveillance interval recommendations.

Smoking is Associated with Higher Disease-related Costs and Lower Health-related Quality of Life in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. RESULTS: In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (€7,905 [95% confidence interval €6,234 - €9,864] vs €6,017 [€5,186 - €6,946] in never-smokers and €5,710 [€4,687 - €6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years (€ 5,135 [95% CI €4,122 - €6,303] vs €9,342 [€6,010 - €12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. CONCLUSIONS: Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.

Consequences of CT colonography in stenosing colorectal cancer.

BACKGROUND: In patients with stenosing colorectal cancer (CRC), visualization of the entire colon prior to surgery is recommended to exclude synchronous tumors. Therefore, most centers combine computed tomographic colonography (CTC) with staging CT. The aims of this study were to evaluate the yield and clinical implications of CTC. METHODS: In this multicenter retrospective study, patients with stenosing CRC that underwent CTC and subsequent surgery between April 2013 and November 2015 were included. Result of the CTC, its influence on the surgical treatment plan, and final histology report were evaluated. RESULTS: One hundred sixty-two patients with stenosing CRC were included. Nine (5.6 %) synchronous cancers proximal to the stenosing tumor were suspected with CTC. In four of nine patients, the CTC did not change the primary surgical plan because the tumors were located in the same surgical segment. In five of nine patients, CTC changed the surgical treatment plan. Three of these five patients underwent an extended resection and the presence of the tumors was confirmed. Two of these three synchronous CRCs were also visible on abdominal staging CT. In the other two patients, the result of CTC was false positive which led to an unnecessary extended resection in one patient. CONCLUSION: The yield of CTC was relatively low. In only three patients (1.9 %), CTC correctly changed the primary surgical plan, but in two of them, the tumor was also visible on abdominal staging CT. Moreover, in two patients, CTC was false positive. The clinical value of CTC in stenosing CRC appears to be limited.

Smoking is Associated With Extra-intestinal Manifestations in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD. RESULTS: In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1-2 years; Groningen cohort, within 1 year). CONCLUSIONS: There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.

Esophageal motor responses to increasing adjustment of an implanted gastric band.

BACKGROUND: The adjustable gastric band is an effective surgical treatment to induce weight loss in patients with morbid obesity. We aimed to assess the effects of band placement and stepwise adjustment on esophageal motility, using high-resolution manometry (HRM). METHODS: Patients underwent esophageal HRM before and 6 weeks after gastric band placement. During postoperative assessment, HRM was combined with intraband pressure measurement at increasing filling volumes. KEY RESULTS: In total, 15 patients were studied. Mean DCI (±SD) decreased from 1085.3 ± 1064.1 mmHg s(-1)  cm(-1) before to 507 ± 347.2 mmHg s(-1)  cm(-1) (P = 0.015) after band placement, mean IBP from 10.7 ± 1.7 mmHg to 7.7 ± 1.6 mmHg (P = 0.01). Stepwise band adjustment from 1 to 8 mL had an immediate and profound effect on swallow-induced esophageal contractions: DCI increased from 766 ± 590.4 to 7231 ± 6298.1 mmHg s(-1)  cm(-1) , IBP from 4.3 mmHg to 31.1 ± 17.3 mmHg, and intraband pressure increased from -109.1 ± 60.6 mmHg to 150.2 ± 65 mmHg. During band filling with volumes >5 mL, upward displacement of the LES was observed, indicative of shortening of the esophagus; the distance between the UES and LES decreased from 23.5 ± 1.3 cm at 0 mL to 19.9 ± 2 cm at 8 mL. CONCLUSIONS & INFERENCES: Stepwise gastric band adjustment leads to immediate enforcement of esophageal peristalsis associated with an increase in intrabolus pressure and with pronounced esophageal shortening. Subjects who lack these responses to outflow obstruction may be more prone to dysphagia after band placement.

Systematic review: the effects of conservative and surgical treatment for obesity on gastro-oesophageal reflux disease.

BACKGROUND: Incidence rates of both obesity and gastro-oesophageal reflux disease (GERD) are increasing, particularly in the Western world. It has been suggested that GERD symptoms may be improved by weight reduction. AIM: To review the literature on the effect of various weight reducing modalities on manifestations of GERD in obese patients. METHODS: A literature search was performed using PubMed, EMBASE and the Cochrane Library, combining the words obesity and gastro-oesophageal reflux with bariatric surgery, diet, lifestyle intervention and weight loss. RESULTS: With regard to diet/lifestyle intervention (conservative), four of seven studies reported an improvement of GERD. For Roux-en-Y gastric bypass, a positive effect on GERD was found in all studies, although this was mainly evaluated by questionnaires. In contrast, for vertical banded gastroplasty, no change or even an increase of GERD was noted, whereas the results for laparoscopic adjustable gastric banding were conflicting. CONCLUSIONS: Dietary and lifestyle intervention may improve GERD in obese patients; however, the most favourable effect is likely to be found after bariatric surgery, especially after Roux-en-Y gastric bypass. Future studies need to elucidate for which GERD patients laparoscopic adjustable gastric banding might have a beneficial effect and how they can be identified preoperatively.

What is the appropriate screening protocol in Lynch syndrome?

INTRODUCTION: Lynch syndrome families have a substantial risk of developing colorectal cancer (CRC). The recommended surveillance protocol includes colonoscopy every 2 years from age 20-25 years. It is yet unknown whether annual screening of patients aged 40-60 years is more effective than bi-annual screening, whether patients who had an adenoma removed should be re-examined after a year and whether surveillance of second-degree relatives is indicated. The aim of this study was to address these issues. METHODS: All carriers of a mismatch repair gene mutation who participated in the surveillance program were selected from the Dutch Lynch syndrome registry. The results of colonoscopy were prospectively collected. RESULTS: A total of 666 mutation carriers were identified in 110 families. Fourty-one CRCs were detected during endoscopic follow-up, of which 34 (83%) were diagnosed between age 40 and 60 years. In five of 34 patients, CRC was diagnosed within 1 year after colonoscopy, eight cancers were diagnosed between 1 and 2 years and the remaining tumors more than 2 years after colonoscopy. All eight CRCs detected between 1 and 2 years were at local stage. At least one adenoma was diagnosed at 141 examinations. The risk of developing CRC during follow-up in carriers with an adenoma was similar as in carriers without an adenoma at the previous colonoscopy. 280 parent-child couples with at least one Lynch syndrome-related carcinoma were identified in 110 families. In only 19 (6.8%) of these couples, CRC developed earlier in the child than an Lynch syndrome-associated cancer in the parent. CONCLUSION: The current surveillance protocol, i.e., bi-annual colonoscopy in first-degree relatives independent of age and endoscopic findings, appears to be appropriate.

Prospective risk assessment of endoscopic retrograde cholangiography in patients with primary sclerosing cholangitis. Dutch PSC Study Group.

BACKGROUND AND STUDY AIMS: Direct endoscopic retrograde cholangiopancreatography (ERCP) has become the standard for establishing the diagnosis of primary sclerosing cholangitis (PSC), while endoscopic procedures play an increasingly important therapeutic role. However, many believe that this procedure carries a significant risk of infection and other complications. We assessed the incidence of complications within 1 week of ERCP in patients with PSC. PATIENTS AND METHODS: In a multicenter study, patients who underwent ERCP for (suspected) PSC were prospectively followed for the occurrence of complications after the procedure. RESULTS: A total of 106 ERCPs performed in 83 patients were evaluated. Complications occurred on ten occasions (9%): pancreatitis (n = 3), cholangitis (n = 2), increase of cholestasis (n = 2), postsphincterotomy bleeding (n = 1), cystic duct perforation (n = 1), and venous thrombosis (n = 1). All complications resolved quickly with proper therapy. Complications were more likely when ERCP was done to evaluate specific complaints such as jaundice or recurrent cholangitis (9/59) than after a purely diagnostic ERCP (1/47 relative risk [RR] 7.2, 95% confidence interval [CI] 1.00 to 153). Therapeutic interventions performed during ERCP (e.g. placement of endoprosthesis, dilation of strictures) also increased the risk of postprocedural complications (RR 4.5, 95 % CI 0.94 to 30). CONCLUSIONS: ERCP is a safe method for establishing the diagnosis of PSC in asymptomatic patients (2 % complication rate). Although ERCP in symptomatic patients carries a higher risk (14%), this can be justified by the benefits of endoscopic therapy.

Effects of ursodeoxycholic acid therapy on in vitro gallbladder contractility in patients with cholesterol gallstones.

During treatment with ursodeoxycholic acid (UDCA), the fasting gallbladder volume increases by a yet unknown mechanism. The present study tests whether in vitro human gallbladder contractility in response to acetylcholine and cholecystokinin is affected by UDCA therapy. Gallbladder tissue was obtained from 15 patients treated with UDCA (10 mg/kg/day) during three weeks prior to surgery, and from 15 comparable patients not treated. Data were correlated with in vivo contractility, bile composition, and gallbladder wall inflammation. The inflammation score was lower in the treated patient group. UDCA treatment enhanced gallbladder contractility in vitro: Dose-response curves for acetylcholine and cholecystokinin were both shifted to the left, and the maximal contractile stress generated in response to cholecystokinin was higher in the treated group, whereas the maximal acetylcholine-induced stress was not increased. Maximal cholecystokinin-induced stress correlated positively with fasting gallbladder volume and negatively with the biliary cholesterol saturation index, but not with bile salt hydrophobicity or gallbladder wall inflammation score. In conclusion, UDCA treatment improves in vitro gallbladder contractility, possibly related to a reduced biliary cholesterol saturation. Increased fasting gallbladder volumes during UDCA treatment thus do not appear to result from decreased gallbladder muscle contractile strength.

Ursodeoxycholic acid therapy for primary sclerosing cholangitis: results of a 2-year randomized controlled trial to evaluate single versus multiple daily doses.

BACKGROUND/AIMS: Ursodeoxycholic acid has been reported to be of potential benefit for primary sclerosing cholangitis but little is known about the long-term biochemical, histological and radiological efficacy or the optimum frequency of ursodeoxycholic acid administration. METHODS: A 2-year multicentre randomised controlled trial was initiated to assess the effects of ursodeoxycholic acid (10 mg kg(-1).d(-1), given in either single or multiple daily doses, on symptoms, serum liver tests, cholangiographic and histological findings and the occurrence of treatment failure. Liver biopsies were taken and endoscopic retrograde cholangiography was performed at entry and after 2 years; follow-up examinations were at 3-month intervals. Treatment failure was defined as death, liver transplantation, 4-fold increase in serum bilirubin, variceal bleeding, de novo ascites or cholangitis. Actuarial survival was compared with predicted survival using the revised Mayo natural history model for primary sclerosing cholangitis. RESULTS: Forty-eight patients were enrolled. In one case, ursodeoxycholic acid had to be discontinued because of gastro-intestinal complaints. No other side-effects were observed. After 2 years of follow-up, treatment was not associated with a beneficial effect on either symptoms or liver histology. Serum liver tests (alkaline phosphatase, y-glutamyl transferase, aspartate aminotransferase) improved significantly in both groups, while serum bilirubin (which was near normal at entry) and IgG remained stable. No major changes in radiographic bile duct appearance seemed to be present. After 2 years, actuarial survival was 91% (95 CI 83%-99%), which is comparable to the predicted 97% survival rate. Treatment failure occurred in 15% of cases. No significant differences in any of the study endpoints (symptoms, serum liver tests, cholangiographic findings, histology, disease progression) were found between the two groups. CONCLUSIONS: Ursodeoxycholic acid is well tolerated in primary sclerosing cholangitis. Significant effects on biochemical parameters were found and symptoms, bilirubin and histology did not deteriorate. No advantage of a multiple daily dose over a single dose was observed.

Low-dose versus high-dose ursodeoxycholic acid in cystic fibrosis-related cholestatic liver disease. Results of a randomized study with 1-year follow-up.

BACKGROUND: Ursodeoxycholic acid (UDCA) is beneficial in cholestasis related to cystic fibrosis (CF). High-dose treatment has been recommended to compensate for bile salt malabsorption. We compared the results of low-dose (10 mg/kg/day) and high-dose (20 mg/kg/day) UDCA treatment on liver biochemistry after 3 and 12 months' treatment. METHODS: Thirty CF patients (age > 5 years) with biochemical cholestasis and compensated liver disease were randomized for low-dose (n = 17) or high-dose (n = 13) UDCA. Baseline clinical variables were comparable. RESULTS: After 1 year one patient had died of liver failure (low dose), and three had dropped out because of pruritus (one in each group) or personal choice (low dose). In the high-dose group improvement in gamma-glutamyl transferase values was more pronounced after 3 months and 1 year (P < 0.004), and improvement of alanine aminotransferase was better after 1 yer (P < 0.02). Improvement of alkaline phosphatase and aspartate aminotransferase was comparable. Complete normalization of liver enzymes and bilirubin occurred more often in the high-dose group. CONCLUSION: High-dose UDCA induces a better response of liver biochemistry values than low-dose UDCA in CF patients with cholestatic liver disease.

[No routine antibiotic prophylaxis necessary in endoscopic retrograde cholangiopancreatography]. / Geen routinematige antibiotische profylaxe nodig bij endoscopische retrograde cholangiopancreaticografie.

Acute cholangitis is a serious complication and cause of death in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Some centres have adopted a policy of administering antibiotics before every ERCP procedure. The results of a recent clinical trial failed to support this policy. Antibiotic prophylaxis should be restricted to patients expected to develop incomplete drainage of the bile duct and to endocarditis prophylaxis.

Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance. AIM: The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated. METHODS: Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg-1 day-1) in a single dose at bed time (n = 13) or in three divided gifts with meals (n = 14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between. RESULTS: Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean +/- SEM) was 40.1 +/- 2.4 in the single dose group vs 40.8 +/- 2.8 in the multiple dose group (p = NS) and was positively correlated with biochemical improvement (AP: r = 0.47, p = 0.02; GGT: r = 0.58, p = 0.002; ASAT: r = 0.67, p = 0.002; ALAT: r = 0.52, p = 0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens. CONCLUSION: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.

Increased gall bladder volume in primary sclerosing cholangitis.

BACKGROUND: The diagnosis of primary sclerosing cholangitis (PSC) requires invasive procedures such as liver biopsy and endoscopic retrograde cholangiography (ERC). Sonographic measurement of fasting gall bladder volume, which has been reported to be enlarged in PSC, could serve as a non-invasive screening test. METHODS: Fasting gall bladder volume was studied in patients with PSC (n = 24), primary biliary cirrhosis (PBC, n = 13), liver cirrhosis due to other causes (n = 18), ulcerative colitis (n = 15), and healthy controls (n = 23). Meal induced gall bladder emptying was studied in patients with PSC, patients with PBC, and healthy controls. RESULTS: In patients with PSC gall bladder volume was greatly enlarged (72.9 (SEM 3.7) ml) compared with healthy controls (25.4 (1.7) ml, and patients with PBC (30.9 (2.7) ml), liver cirrhosis (31.3 (4.0) ml) or ulcerative colitis (25.8 (2.0) ml) (p < 0.0005 v all). In four patients with PSC the gall bladder wall was irregularly thickened (> 4 mm) as previously described in PSC. Postprandial residual fractions (% of fasting volume) were comparable between patients with PSC (17.5 (3.7)%) and those with PBC (23.6 (7.1%) and healthy controls (12.7 (2.3)%) Although gall bladder emptying seems normal, increased biliary pressure in patients with PSC cannot be excluded. CONCLUSION: Apart from wall thickening, patients with PSC often present with enlargement of the gall bladder. Sonographic determination of fasting gall bladder volume may be a useful, non-invasive, and easy to perform tool in the evaluation of patients suspected of having PSC.

Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy.

Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment in selected gallstone patients, but stone recurrence is a major drawback. Factors potentially influencing gallstone clearance and recurrence were studied in 84 patients in whom stone dissolution was diagnosed after ESWL plus bile salt therapy for initial solitary (n = 55) or multiple (n = 29) radiolucent stones. Apolipoprotein E (apoE) genotyping and gallbladder motility (sonography) were studied in a representative subgroup of patients (n = 50). The median follow-up after ESWL was 36 months (range, 4.5-67 months). Gallstone clearance was achieved after 8.7 months (range, 0.2-30 months). Independent factors significantly enhancing gallstone clearance were the presence of E4 allele; small initial gallstone size and number; effectiveness of fragmentation; and good gallbladder emptying (P = .002). Gallstone recurrence was seen in 30 patients after 18.6 months (range, 1.0-50 months). Cumulative gallstone recurrence rate (life-table analysis) was 15% within 1 year, increasing to 60% within 5.5 years. Although the probability of gallstone recurrence tended to be smaller in patients with initial solitary stones than in those with multiple stones during early follow-up, differences disappeared after long-term follow-up. Effective gallbladder emptying (residual volume < or = 6 mL) and apolipoprotein E4 (apoE4) independently influenced gallstone recurrence. Recurrence rate was higher (log rank test, P = .037) in those patients who were homozygous and heterozygous for the E4 allele compared with the individuals who were not expressing the apoE4 allele. Accordingly, there was an overrepresentation of the allele frequency for E4 in the group with gallstone recurrence (P =.03). Patients with small postprandial residual gallbladder volumes (

Risk of primary sclerosing cholangitis is associated with nonsmoking behavior.

BACKGROUND & AIMS: Seventy percent of patients with primary sclerosing cholangitis (PSC) have concomitant ulcerative colitis. Smoking and previous appendectomy may protect against ulcerative colitis. The aim of this study was to examine these factors in patients with PSC. METHODS: Fifty-nine patients with PSC, 130 patients with ulcerative colitis and normal liver biochemistry, and 197 control subjects were interviewed about smoking behavior and history of appendectomy. RESULTS: There were less current smokers in the PSC and ulcerative colitis groups than in the control group (19%, 12%, and 38%, respectively). The resulting odds ratio for current smoking was 0.37 (95% confidence interval, (0.18-0.76) in the PSC group and 0.23 (95% confidence interval, 0.13-0.41) in the ulcerative colitis group. Percentage of persons who ever smoked was also significantly less in the PSC group (41% vs. 56% in the control group). Frequency of previous appendectomy in the PSC and ulcerative colitis groups was not significantly different from that of controls (19%, 9%, and 14%, respectively). CONCLUSIONS: Smoking but not previous appendectomy is associated with decreased risk of PSC.

Cholestatic liver diseases: new strategies for prevention and treatment of hepatobiliary and cholestatic diseases.

Based on proceedings of the 75th Falk Symposium in Maastricht (The Netherlands) on cholestasis and gallstone disease, recent developments in this field are highlighted. New ideas on bile and gallstone formation as well as effect of cholestasis on the handling of bilirubin and bile salts are presented. Special attention is paid to the latest data concerning ductopenic liver diseases with emphasis on therapy with ursodeoxycholic acid (UDCA).

Rationale for therapy with ursodeoxycholic acid in patients with cholestatic liver disease.

Ursodeoxycholic acid is increasingly used in the treatment of a variety of cholestatic diseases such as primary biliary cirrhosis. The present article summarizes current understanding of the mechanism of action of ursodeoxycholic acid in these diseases. Apart from a direct hepatoprotective effect, ursodeoxycholic acid also influences the enterohepatic circulation with decreased ileal reabsorption and increased faecal excretion of potentially hepatotoxic endogenous bile salts. In addition, a cholehepatic shunt mechanism and immune modulating effects may also be important.

Therapy with ursodeoxycholic acid in cholestatic liver disease.

Ursodeoxycholic acid (UDCA) has beneficial effects on symptoms, liver biochemistry and, possibly, liver histology in primary biliary cirrhosis and other cholestatic liver diseases. UDCA may exert these beneficial effects by a direct hepatoprotective effect, by influencing the enterohepatic circulation of endogenous bile salts, by enhancing bile flow through a cholehepatic shunt mechanism or by immune modulation. In the present article, established and potential indications for UDCA are reviewed.