Ursodeoxycholic acid enhances fractional calcium absorption in primary biliary cirrhosis.

Bone disease is a frequently reported complication in primary biliary cirrhosis (PBC), but its pathogenesis is poorly understood. Calcium malabsorption has been considered as an important contributing factor. Ursodeoxycholic acid (UDCA) is the treatment of choice in PBC, improving survival, but its effect on calcium absorption is unknown. In this study, we have measured fractional calcium absorption, using a single isotope method, in a group of female PBC patients (median age: 60 years, range: 46-78 years) and age-matched female controls (median age: 58 years, range: 36-74). Bone mineral density (BMD) in PBC patients was significantly lower than age-matched controls (g/cm(2) +/- SEM; lumbar spine: controls 1.139+/-0.028, PBC patients 1.004+/-0.026, p = 0.0028; femoral neck: controls 0.944+/-0.034, PBC patients 0.819+/-0.023, p = 0.0032). Twenty two PBC patients, who were not vitamin D-deficient, were off and on UDCA for approximately 1 month and approximately 8 weeks, respectively. Fractional calcium absorption in PBC patients prior to UDCA treatment (mean +/- SEM, 33.8+/-2.6%) was significantly lower than controls (52.0+/-2.4%, p<0.001). Following UDCA therapy, fractional calcium absorption increased significantly (Off UDCA: 33.1+/-2.6%, On UDCA: 36.6+/-2.5%, p<0.0058). Osteocalcin levels were significantly raised in the PBC group (mean +/- SEM, ng/ml, 41.4+/-2.02) compared to controls (31.1+/-2.64, p = 0.002). There were no differences in parathyroid hormone (PTH) or 25-hydroxyvitamin D levels between these two groups or following UDCA therapy. In conclusion, we found that PBC patients display low spinal and femoral neck BMD, reduced fractional calcium absorption, and elevated plasma osteocalcin. The calcium malabsorption is corrected partially by UDCA therapy. Long-term studies are required to determine whether this effect can be sustained, and whether a sustained increase in fractional calcium absorption can translate into a favorable change in bone strength in patients with PBC.

Review article: faecal markers in the assessment of activity in inflammatory bowel disease.

The fundamental pathological process behind ulcerative colitis and Crohn's disease is intestinal inflammation. As the precise cause of this is not yet completely understood, current treatment strategies are aimed at reducing or eliminating the inflammation. Endoscopic examination and histological analysis of biopsy specimens remain the 'gold standard' methods for detecting and quantifying bowel inflammation; however, these techniques are costly, invasive, and repeated examinations are unpopular with patients. Disease activity questionnaires and laboratory 'inflammatory markers', although widely used, show an unreliable correlation with endoscopy and histology. New markers need to be developed to detect and quantify bowel inflammation. These would be of use diagnostically and also an aid to pharmacological treatment.

Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group.

BACKGROUND: Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization. AIM: To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy. PATIENTS AND METHODS: A total of 154 symptomatic patients with radiolucent stones (< or = 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6-monthly oral cholecystography and ultrasonography for up to 24 months. RESULTS: Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side-effects or dropout rate. Complete gallstone dissolution on an intention-to-treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively. CONCLUSION: There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.

Postprandial refilling and turnover: specific gallbladder motor function defects in patients with gallstone recurrence.

BACKGROUND AND AIMS: Impaired gallbladder motor functions are important in the pathogenesis of primary cholesterol gallstones, and possibly in the pathogenesis of recurrent gallstones. By using ultrasonography and cholescintigraphy simultaneously, we recently defined new parameters of gallbladder motor function (postprandial refilling and turnover in addition to emptying), which were markedly impaired in gallstone patients. The aim of this study was to assess the value of these new parameters in distinguishing patients with from those without gallstone recurrence. METHODS: We studied 11 patients with gallstone recurrence, 11 without gallstone recurrence (at least 40 months after complete dissolution by oral bile acids) and 11 healthy controls. Simultaneous measurements of gallbladder volume (ultrasound) and gallbladder counts (gamma-camera scintigraphy) were carried out in the fasting state and at 10 min intervals following meal ingestion, for a period of 90 min. Gallbladder refilling, turnover of bile and turnover index were calculated, as well as gallbladder emptying by both cholescintigraphy and ultrasound. RESULTS: Patients with gallstone recurrence had reductions in gallbladder emptying, postprandial refilling and gallbladder bile turnover. They also had a significant reduction in the turnover index (1.7 +/- 1.4) compared to controls (3.5 +/- 0.3, P < 0.01) and to patients without gallstone recurrence (3.1 +/- 1.5, P < 0.05). Patients without gallstone recurrence had only a small reduction in emptying and no reduction in postprandial refilling or turnover compared to controls. CONCLUSIONS: We conclude that impairment of gallbladder emptying persists in all patients after gallstone dissolution, albeit to a more pronounced extent in patients with recurrence; but that impairment of postprandial refilling and turnover are specific defects in patients with recurrence.

Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group.

OBJECTIVE: To assess risk factors for gallstone recurrence following non-surgical treatment. DESIGN: A prospective follow-up of a multicentre cohort of post-dissolution gallstone patients. SETTING: Six gastroenterology units in the UK and Italy. PARTICIPANTS: One hundred and sixty-three patients with confirmed gallstone dissolution following non-surgical therapy (bile acids or lithotripsy plus bile acids), followed up by ultrasound scan and clinical assessment at 6-monthly intervals for up to 6 years (median, 25 months; range, 6-70 months). OUTCOME MEASURES: Subject-related variables (sex, age, height, weight, body mass index), gallstone-related variables (number, diameter, presence of symptoms, months to complete stone clearance), treatment modalities (bile acid therapy, extracorporeal shock wave lithotripsy) and follow-up related variables (weight change, use of non-steroidal anti-inflammatory agents, statins, pregnancies and/or use of oestrogens) were assessed by univariate and multivariate analysis as putative risk factors for gallstone recurrence. RESULTS: Forty-five gallstone recurrences were observed during the follow-up period. Multiple primary gallstones and length of time to achieve gallstone dissolution were the only variables associated with a significant increase in the recurrence rate. Appearance of biliary sludge during follow-up was also significantly related to development of gallstone recurrence. Use of statins or non-steroidal anti-inflammatory agents did not confer protection against recurrence. CONCLUSIONS: Patients with primary single stones are the best candidates for non-surgical treatment of gallstones, because of a low risk of gallstone recurrence. The positive association of recurrence with biliary sludge formation and time to dissolution of primary stones may provide indirect confirmation for the role of impaired gallbladder motility in the pathogenesis of this condition.

Progression of Gastric Mucosal Dysplasia of the Postgastrectomy Stomach.

Gastric cancer, if diagnosed at the symptomatic stage, has a poor prognosis, with an overall 5 year survival of about 5%. The surgical treatment of early gastric cancer increases this 5-year survival rate to 90%. In Japan, endoscopic surveillance has increased the proportion of gastric cancer detected at an early stage from 15% in 1960 to 50% in 1985, and the overall 5 year survival has been increased from 35% to 70%. Mass screening in Japan is worthwhile because the incidence of gastric cancer is about 80 cases per 100,000 population per annum (age standardized). But in other countries where the incidence is much lower the case for mass screening is weak and selective screening of those at high risk is advocated.

Progression of gastric mucosal dysplasia of the postgastrectomy stomach.

Gastric cancer, if diagnosed at the symptomatic stage, has a poor prognosis, with an overall 5 year survival of about 5%. The surgical treatment of early gastric cancer increases this 5-year survival rate to 90%. In Japan, endoscopic surveillance has increased the proportion of gastric cancer detected at an early stage from 15% in 1960 to 50% in 1985, and the overall 5 year survival has been increased from 35% to 70%. Mass screening in Japan is worthwhile because the incidence of gastric cancer is about 80 cases per 100,000 population per annum (age standardized). But in other countries where the incidence is much lower the case for mass screening is weak and selective screening of those at high risk is advocated.

Demonstration and partial characterisation of phospholipid methyltransferase activity in bile canalicular membrane from hamster liver.

BACKGROUND/AIMS: Methylation of phosphatidylethanolamine to phosphatidylcholine predominantly takes place in mitochondrial-associated membrane and the endoplasmic reticulum of the liver. The transport of the phospholipids from endoplasmic reticulum to the bile canalicular membrane is via vesicular and protein transporters. In the bile canalicular membrane a flippase enzyme helps to transport phosphatidylcholine specifically to the biliary leaflet. The phosphatidylcholine then enters the bile where it accounts for about 95% of the phospholipids. We postulated that the increased proportion of phosphatidylcholine in the bile canalicular membrane and the bile compared to the transport vesicles may be due to a methyltransferase activity in the bile canalicular membrane which, using s-adenosyl methionine as the substrate, converts phosphatidylethanolamine on the cytoplasmic leaflet to phosphatidylcholine, which is transported to the biliary leaflet. The aim of our study was to demonstrate and partially characterise methyltransferase activity in the bile canalicular membrane. METHODS: Organelles were obtained from hamster liver by homogenisation and separation by sucrose gradient ultracentrifugation. These, along with phosphatidylethanolamine, were incubated with radiolabelled s-adenosyl methionine. Phospholipids were separated by thin-layer chromatography and radioactivity was counted by scintigraphy. RESULTS: We demonstrated methyltransferase activity (nmol of SAMe converted/mg of protein/h at 37 degrees C) in the bile canalicular membrane of 0.442 (SEM 0.077, n=8), which is more than twice that found in the microsomes at 0.195 (SEM 0.013, n=8). The Km and pH optimum for the methyltransferase in the bile canalicular membrane and the microsomes were similar (Km 25 and 28 microM, respectively, pH 9.9 for both). The Vmax was different at 0.358 and 0.168 nmol of SAMe converted/mg of protein/h for the bile canalicular membrane and the microsomes, respectively. CONCLUSION: The presence of the methyltransferase activity in the bile canalicular membrane may be amenable to therapeutic manipulation.

Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver function tests and prolongs survival in primary biliary cirrhosis (PBC). The dose of 10- 15 mg/kg/day used in the large trials has largely been based on that used for gallstone dissolution. The only dose-response study of UDCA in PBC suggested that a dose of 8 mg/kg/day was the most efficacious. However, disease stage of the patients was not known, higher doses of UDCA were not tried and there was no 'washout period' between the different doses. The aim of this study was to determine the optimum dose of UDCA in early-stage PBC (stage 1 and 2). METHODS: Twenty-four biopsy-proven early-stage PBC patients (one male, 23 female) received five doses of UDCA (0, 300, 600, 900, 1200 mg/day) each for 8 weeks with 4-week washout periods between doses. Symptoms (pruritus, fatigue, diarrhoea) were assessed on a four-point scale (none, mild, moderate, severe). Liver function tests (LFTs) were performed using conventional methods, and serum bile acids were measured using gas liquid chromatography. RESULTS: The dose of 900 mg/day produced the greatest enrichment of UDCA in serum bile acids; although there was no difference in the enrichment of UDCA between the different doses. There was a trend towards normalization of the abnormal LFTs in a dose-dependent manner (for y-glutamyl transferase (yGT), alkaline phosphatase (ALP), alanine transaminase (ALT) and IgM). Multi-factorial analysis showed that UDCA treatment, irrespective of dose, was significantly better than placebo for all the variables. The 900 and 1200 mg doses were better than both 300 and 600 mg using yGT and total bilirubin as variables, better than 300 mg using ALP and IgM as variables, and better than 600 mg using albumin as a variable. No variables showed a significant difference between 900 and 1200 mg. CONCLUSION: The optimum dose of UDCA is 900 mg/day (equivalent to 13.5 mg/kg/day).

Prescribing habits in primary biliary cirrhosis: a national survey.

BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. A number of drugs have been used in its treatment, but only ursodeoxycholic acid (UDCA) has been shown to improve survival. Our aims were to determine the current prescribing habits in PBC of all practising gastroenterologists in the UK. METHODS: A postal questionnaire was sent to 454 gastroenterologists in 1996, followed by a second questionnaire a month later to the non-responders. RESULTS: Of 454 doctors sent questionnaires, 379 (83%) replied. Of these, 58 were excluded from further analysis as they were not practising gastroenterologists. There are an estimated 4337 patients with PBC being seen by gastroenterologists in hospitals. Of these, only 1376 (32%) are being seen in liver units. Ninety-one per cent of gastroenterologists look after patients with PBC (median 10 patients, range 1-500). Ninety-five per cent of gastroenterologists prescribe UDCA but there is a large dose range (median 11.5 mg/kg/day, range 1.5-23.1). Of these, 93% also prescribe cholestyramine. Only 45 (14%) gastroenterologists prescribed other treatments for PBC (13 colchicine, 24 steroids, nine penicillamine, 13 immunosuppressants). Only 53 (17%) treat the symptoms/complications of PBC (37 fat-soluble vitamins, 15 calcium, six bisphosphonates, one hormone replacement therapy, 10 antihistamines, 10 rifampicin). CONCLUSIONS: UDCA is being prescribed for PBC by the majority of practising gastroenterologists but over a wide dose range. Very few gastroenterologists are using preventive treatment for osteoporosis in this high-risk group. Other treatments, as yet unproven in trials, are being prescribed by a minority of gastroenterologists.

Relationship between Helicobacter pylori, gastric parietal cell antibodies and heat shock proteins.

BACKGROUND: The relationship between Helicobacter pylori and autoimmune (type A) gastritis is unclear. Infections may trigger autoimmune phenomena but the underlying mechanisms are unknown. AIM: To determine the relationships between H. pylori infection and gastric parietal cell antibodies (PCA), and PCA and heat shock protein (HSP) antibody. METHODS: Fifty-five serum samples positive for PCA, 22 males and 33 females (median age 61 years, range 29-108 years) were compared with 60 control samples negative for PCA, 24 males and 36 females (median age, 48 years, range 11-91 years). H. pylori infection and HSP65K antibodies were determined by enzyme-linked immunosorbent assay. CagA and VacA status were determined by Western blotting. RESULTS: The prevalence of H. pylori was higher in PCA-positives than controls, 29/55 [53%, 95% confidence interval (CI) 39-66%] versus 13/60 (22%, 95% CI 12-34); P= 0.0009. Age was not a confounding factor. Odds ratio for PCA seropositivity if H. pylori-positive was 4.0 (1.79-9.07), P= 0.003. There was an interaction between age and H. pylori, particularly in younger patients. CagA strains were less common in PCA-positives than controls, 10/29 (35%, 95% CI 19-54) versus 9/13 (69%, 39-91), P< 0.05. HSP65K antibodies were elevated in H. pylori infection but to a similar degree for both PCA-positives and controls. CONCLUSION: H. pylori, particularly CagA-negative strains, are associated with autoimmune gastritis and may be implicated in the pathogenesis of autoimmune (type A) gastritis, particularly in younger persons.

Determinants of prescribing costs for ulcer-healing drugs and upper gastrointestinal endoscopy in general practice.

BACKGROUND: Prescriptions for ulcer-healing drugs (UHDs) and endoscopy costs represent major expenditures for dyspepsia in primary care. Healthcare expenditure for dyspepsia could be better understood if the factors contributing to the expenditure for dyspepsia could be identified. AIMS: To determine whether prescribing costs of UHDs and use of endoscopy in general practice were related to the characteristics of the practices or to the characteristics of the population it served DESIGN: Twenty-seven GP practices in south London were studied prospectively over 6 months. Prescribing costs for UHDs were obtained from PACT and data for endoscopies from hospital PAS systems. Demographic data on practice size, age and sex distribution were obtained from the district FHSA. The Jarman index, Townsend score and proportion of ethnic minorities in the practice population were determined from the Population Census Survey. RESULTS: Total expenditure on UHDs by the 27 practices was Pound Sterling 1 million per annum and endoscopy rate was 1.1% per annum. Expenditure on UHDs was negatively correlated with practice size (P = 0.006) and use of open access endoscopy (P < 0.005) and positively correlated with number of patients aged over 45 years (P = 0.007). Endoscopy use was positively correlated with proportion of ethnic minorities (P = 0.008) and negatively with male:female ratio (P = 0.049). CONCLUSIONS: Resource utilization on dyspepsia in general practice is determined by both practice and population characteristics.

Variation in taste of topical lignocaine anaesthesia for gastroscopy.

AIM: To study the distribution and determinants of taste variation for lignocaiine spray (Xylocaine; Astra Pharmaceuticals, King's Langley, UK). METHODS: Sixty-nine patients (male:female 49:20, mean age 48.5 years) attending for open access upper gastrointestinal endoscopy were studied. Taste perceived after applying 4 doses (40 mg) of lignocaine spray to the oro-pharynx was recorded prior to endoscopy. RESULTS: 37/69 (54%, 95% CI: 41-66%) perceived the taste of the lignocaine spray as bitter. whilst 24/69 (35%, 95% CI: 24-47%) and 6/69 (9%, 95% CI: 3-18%) perceived the taste as either fruity/sweet or tasteless. The variation in taste did not correlate with either demographic features or H. pylori inflection, but duodenal ulceration was slightly more common amongst bitter tasters. CONCLUSION: The taste of lignocaine is not uniform, but the basis of this variability is uncertain.

Dissolution of gallbladder stones with methyl tert-butyl ether and stone recurrence: a European survey.

Since there are now several ways to treat symptomatic gallstone disease, one is able to select treatment on the basis of the patient's comfort, the practicability, effectiveness, and side effects of the technique, and the relative costs. In order to assess the present status of contact dissolution with methyl tert-butyl ether with regard to these aspects, the present enquiry reports the data of 21 European hospitals. Eight hundred three patients were selected for contact litholysis of cholesterol gallbladder stones using methyl tert-butyl ether. Percutaneous transhepatic puncture of the gallbladder was performed under x-ray or ultrasound guidance. Dissolution rate, side effects, and treatment times of 268 patients from one single center were compared to those of 535 patients from the other 20 centers. Two hundred sixty-four patients were followed for five years to assess stone recurrence. Physicians were asked how they assessed the expenditure of the method, the discomfort to the patients, and the staffing situation. Patients were asked to indicate their acceptance on an analog scale. Puncture was successful in 761 (94.8%) patients. Prophylactic administration of antibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludge remained in the gallbladder. The most severe complication was bile leakage, which led 12 (1.6%) patients to have elective cholecystectomy. Toxic injuries due to the ether were not reported. Method-related lethality amounted to 0%, 30-day-lethality to 0.4%. Stone recurrence rate was about 40% in solitary stones and about 70% in multiple stones over five years. Patients with multiple stones developed recurrent stones almost twice as often as those with solitary stones. The probability of stone recurrence in patients with sludge in the gallbladder after catheter removal was not statistically significantly different from those without sludge. Seventy to 90% of the centers found the puncture to be simple and not distressing for patients and the relation between expenditure and therapeutic success to be acceptable. The acceptance of contact litholysis by the patients was excellent. Contact litholysis when applied by an experienced team provides real advantages in the treatment of gallstone disease. The method is technically simple, well accepted by the patients, and can be easily applied in community hospitals. Contact litholysis may be of particular value in patients who are not suitable for anesthesia or surgery.

Which Helicobacter pylori-positive dyspeptics are likely to respond symptomatically to empirical H. pylori eradication?

OBJECTIVE: To identify which Helicobacter pylori-positive dyspeptic patients have an increased likelihood of having peptic ulcer and may thus be more likely to benefit from empirical H. pylori eradication therapy. METHODS: 622 out of 740 consecutive dyspeptic subjects (median age 45 years, range 14-91, 51% male) attending for rapid access endoscopy were eligible for the study. Demographic data and endoscopic findings were recorded. H. pylori status was determined by urease and histology. RESULTS: In all age groups, peptic ulcers were commoner in males than females [44% (85/195) vs 23% (32/139), P < 0.001] and in smokers than non-smokers [47% (46/97) vs 32% (50/159), P < 0.05]. Males, heavy smokers and those with a family history of peptic ulcer had increased adjusted odds of having a peptic ulcer (2.59, 1.96 and 1.90, respectively). Corresponding odds ratios for those aged under 45 were 2.59, 0.94 and 2.52. In H. pylori-positive dyspepsia, being a male who either smoked heavily or had a family history of peptic ulcer gave a sensitivity and positive predictive value for peptic ulcer of 86 and 45% for all age groups and 85 and 49% for those aged under 45. CONCLUSION: Male H. pylori dyspeptics who smoke >10 cigarettes per day and/or have a family history of peptic ulcer are likely to have peptic ulcer and are thus likely to benefit from empirical eradication therapy.

A randomized trial of endoscopy vs no endoscopy in the management of seronegative Helicobacter pylori dyspepsia.

BACKGROUND: It is unclear whether endoscopy influences the management of Helicobacter pylori negative dyspepsia. AIM: To determine whether endoscopy alters health-care resource utilization, quality of life and symptom outcome in H. pylori seronegative dyspeptic patients aged under 45 years; and to determine which factors predict outcome of symptoms. METHOD: One hundred and fifty-four H. pylori seronegative subjects were randomized to have an endoscopy or no endoscopy before subsequent management by their GPs. Assessment was carried out at 6 months and supplementary information obtained at 12 months. RESULTS: There was no significant difference between the two groups for progression of dyspeptic symptoms (better, same and worse) at 6 months (47%, 46%, 7% vs 43%, 52%, 5%), and at 12 months (55%, 34%, 11% vs 57%, 28%, 15%). Prescriptions were lower in both groups at 6 and 12 months than on entry into the study, independent of endoscopy. Endoscopy did not influence quality of life, visits to GPs and days lost from work. Prognostic factors for symptom resolution at 6 months were lower severity of initial symptoms, non-smoking, non-Caucasians, less anxious patients and those not on acid suppressants. CONCLUSIONS: H. pylori negative dyspeptic patients aged under 45 years without sinister symptoms could be managed without the need of an endoscopy.

Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.

OBJECTIVE: To determine whether serum concentrations of the cytokines tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. DESIGN: A population based cross sectional study. SUBJECTS AND METHODS: 198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. RESULTS: Serum TNF alpha concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNF alpha was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNF alpha, each by approximately 50% (P < 0.05 for TNF alpha, P < 0.1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNF alpha and 36% for IL-6 (P = 0.14 for TNF alpha and P < 0.05 for IL-6). CONCLUSIONS: This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism.

Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: effect of ursodeoxycholic acid and immunosuppressive therapy.

OBJECTIVES: Soluble intercellular adhesion molecule-1 (sICAM-1) is thought to be released by a variety of cells at sites of inflammation, and their serum levels have been used as markers of inflammatory and immune activity. Our aim was to determine the effect of therapy with ursodeoxycholic acid alone and in combination with azathioprine and prednisone on serum sICAM-1 levels in primary biliary cirrhosis. DESIGN/METHODS: Twenty-four patients with primary biliary cirrhosis and 17 healthy subjects were studied. Primary biliary cirrhosis patients received ursodeoxycholic acid for 12 months and were then randomized in a double-blind fashion to receive prednisone and azathioprine, or placebo in addition to ursodeoxycholic acid. RESULTS: sICAM-1 levels were significantly higher in primary biliary cirrhosis patients than healthy subjects and fell by a median of 20% after 12 months' therapy with ursodeoxycholic acid (P<0.0004). Addition of azathioprine and prednisone to ursodeoxycholic acid resulted in a further reduction of sICAM-1 levels by a median of 25% (P< 0.01). Reductions in sICAM-1 were accompanied by improvement in liver function tests but not in the lymphocyte activation marker, soluble interleukin-2 receptor. CONCLUSION: sICAM-1 levels in primary biliary cirrhosis are reduced by ursodeoxycholic acid. Further reductions were achieved by adding prednisone and azathioprine. These reductions probably reflect an improvement in hepatobiliary excretion and a reduction in cellular production of sICAM-1.