Elevated serum PIIINP and laminin in inflammatory bowel disease indicate hepatobiliary and pancreatic dysfunction.

BACKGROUND/AIMS: Levels of S-PIIINP (serum aminoterminal propeptide of type III procollagen) have been shown to be increased in patients with primary sclerosing cholangitis and inflammatory bowel disease. The aim of the study was to investigate the serum concentrations of PIIINP and laminin in inflammatory bowel disease patients, their relationship with inflammatory bowel disease-associated hepatobiliary and pancreatic dysfunction, and to correlate them with clinical, endoscopic, and histologic variables. METHODOLOGY: S-PIIINP and S-laminin were measured in 222 consecutive inflammatory bowel disease patients, who were screened for abnormal liver and pancreatic enzymes and for pancreatic exocrine hypofunction with the p-aminobenzoic acid test (215 patients). The patients with abnormal screening results were further scheduled for endoscopic retrograde cholangiopancreatography, liver biopsy, secretin test and ultrasound. RESULTS: S-PIIINP and S-laminin were abnormally high in 19% and 40% of all inflammatory bowel disease patients, respectively. The elevated levels of the fibrosis markers were associated with laboratory signs of either hepatobiliary or pancreatic disease. Hepatobiliary disease was found in 37 (17%) of inflammatory bowel disease patients, 15 of whom had primary sclerosing cholangitis. The median levels of S-PIIINP and S-laminin were significantly higher in patients with hepatobiliary disease than in those without (P < 0.0001 and P < 0.001, respectively), being most strikingly elevated in primary sclerosing cholangitis. Abnormal pancreatic screening tests were found in 67 (30%) patients. High levels of S-PIIINP and S-laminin were also significantly associated with low values in p-aminobenzoic acid (P < 0.001 and P < 0.005) and secretin (P < 0.01 and P < 0.05) tests, but not with inflammatory bowel disease category, endoscopic or histological disease extent, frequency of bowel resection or actual clinical activity. CONCLUSIONS: In inflammatory bowel disease, increased S-PIIINP and S-laminin are associated with hepatobiliary and pancreatic disorders.

Seroprevalence of Helicobacter pylori infection in inflammatory bowel disease: is Helicobacter pylori infection a protective factor?

BACKGROUND: The mechanisms for the observed low prevalence of Helicobacter pylori infection in inflammatory bowel disease (IBD) are unknown, but might be important for the pathogenesis of IBD. We have studied the seroprevalence of H. pylori in different categories of IBD and evaluated the role of medical therapy, smoking and social status. We also analysed the effect of seropositivity on the age of onset of IBD in order to find possible evidence for the protective effect of the infection. METHODS: We studied 296 (mean age 43 years, range 18-79; women 144) unselected patients with IBD, including 185 with ulcerative colitis (UC). 94 with Crohn disease (CD), and 17 with indeterminate colitis (IC). Seventy healthy age- and sex-matched subjects served as controls. Serum samples were studied for H. pylori antibodies. Detailed clinical history was obtained from patient records and by face-to-face interview. RESULTS: The prevalence of H. pylori infection was lower in IBD patients (24%) than in controls (37%; P = 0.029), and in CD lower (13%) than in UC (30%; P = 0.002). Seropositivity was not related to sulphasalazine treatment or smoking. Age of onset of IBD was higher in seropositive (mean 40 years) than in seronegative patients (30 years: P < 0.001). The age of onset of IBD showed unimodal distribution in H. pylori seronegative patients, with a peak between 30 and 40 years, although there was some evidence of bimodality in CD. In contrast, H. pylori seropositive patients had clear bimodal pattern with peaks at 20-40 and 50-60 years of age. CONCLUSIONS: Our results confirm the low prevalence of H. pylori infection in IBD, and in particular in CD. The significantly higher age of onset and bimodal pattern of age-specific incidence in seropositive IBD patients suggest that H. pylori infection significantly modifies the development of IBD and may have a protective effect.

Elevated pancreatic enzymes in inflammatory bowel disease are associated with extensive disease.

OBJECTIVE: Our aim was to perform a cross-sectional study to estimate the prevalence of elevated pancreatic enzymes in patients with inflammatory bowel disease and to correlate the enzyme activities with clinical, endoscopic, and histological findings. METHODS: Two hundred thirty-seven patients diagnosed with inflammatory bowel disease (IBD), including a subgroup with known hepatobiliary disease, were studied crosssectionally. Serum and urinary pancreatic enzymes were prospectively sampled and compared to endoscopic and histological findings obtained previously. RESULTS: Hyperamylasemia was found in 11% and hyperlipasemia in 7% of the total study group. The corresponding prevalences in patients with Crohn's disease were 17% and 9%, those in ulcerative colitis 9% and 7%, and those in indeterminate colitis 10% and 5%, respectively. High levels of serum amylase and pancreatic isoamylase were associated with extensive colonic disease (p < 0.005) and high histological activity (p < 0.05). Amylase, but not lipase, was significantly elevated in patients with primary sclerosing cholangitis. Smokers showed higher urinary amylase levels than non- and ex-smokers. The use of medication had no influence on the enzyme levels. CONCLUSIONS: Pancreatic enzymes are elevated in a significant proportion of patients with IBD, and the enzyme increase is associated with a more extensive and active disease, and in some cases with primary sclerosing cholangitis.

Hepatobiliary and coexisting pancreatic duct abnormalities in patients with inflammatory bowel disease.

BACKGROUND: We performed a cross-sectional study to evaluate the prevalence of hepatobiliary disease in unselected patients with inflammatory bowel disease (IBD), to estimate the frequency of coexisting cholangiographic and pancreatographic duct abnormalities, and to correlate the findings with clinical, endoscopic, and histologic variables. METHODS: We screened 237 IBD patients for increased liver function values. Further, hepatobiliary evaluation consisted of transabdominal ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), and a liver biopsy. In addition, we evaluated the ERCP findings of patients with abnormal pancreatic screening tests (pancreatic enzymes or para-aminobenzoic acid excretion). RESULTS: Laboratory signs of hepatobiliary disease were found in 37 (16%) of our IBD patients. Abnormal liver test results were commoner in patients with Crohn's disease (CD) than in patients with ulcerative colitis (UC) (30.4% versus 11.2%, P < 0.05), and a similar trend was observed in the frequency of primary sclerosing cholangitis (PSC) in the respective groups of IBD patients. When the ERCP findings were combined with liver histology, 26 (11% of the whole study group) patients with PSC were found, with small-duct disease included. In 23 (10% of the whole study group) patients, definite cholangiographic changes consistent with PSC were found. Eleven (48%) of these showed coexisting pancreatic duct abnormalities. The prevalence of coexisting cholangiographic and pancreatographic duct changes in the whole study group was 4.6%. CONCLUSION: Hepatobiliary disease is at least equally common in patients with UC and CD. Coexisting cholangiographic and pancreatographic duct abnormalities in patients with IBD are relatively frequent and are considered extraintestinal manifestations of IBD.

Pancreatic duct abnormalities and pancreatic function in patients with chronic inflammatory bowel disease.

BACKGROUND: We performed a cross-sectional study to estimate the prevalence of duct abnormalities and exocrine pancreatic dysfunction in an unselected group of patients with inflammatory bowel disease (IBD) and to correlated the findings with clinical, endoscopic, and histologic variables. METHODS: A total of 237 IBD patients were screened for pancreatic enzymes and with a PABA test. Seventy-one (30%) patients with values more than twice the upper normal limit in biochemical tests or with a PABA test < 40% were further evaluated. The pancreatic evaluation included endoscopic retrograde pancreatography, ultrasonography, and a secretin test. The endoscopic and histologic findings were systematically evaluated. RESULTS: The secretin test was completed in 54 patients, and in 10 (19%) it showed a decreased maximal bicarbonate concentration, corresponding to 4% of the whole study group. The pancreatograms of 59 patients were studied. In 20 (34%) patients unequivocal duct abnormalities were found. The prevalence of pancreatic duct abnormalities in IBD was 8.4%. CONCLUSION: Our results show the presence of pancreatic duct abnormalities and exocrine pancreatic insufficiency in some patients with IBD.

Simultaneous solubilization of steroid hormones II: androgens and estrogens.

The simultaneous solubilization of some androgens and estrogens in aqueous polysorbate 40, tetradecyltrimethylammonium bromide, and sodium lauryl sulfate was studied. The solubilizations of estradiol and testosterone were independent of each other in all three association colloids. However, if the estrogen component was ethinyl estradiol, the solubilization was dependent on the addition order. The estrogen precipitates more readily than testosterone in polysorbate 40 and tetradecyltrimethylammonium bromide, but the opposite is true in sodium lauryl sulfate. The simultaneous solubilizations of methyltestosterone or ethisterone with the estrogens tested were different from those of testosterone. The solubilization behavior of the steroids is discussed, starting with the pseudophase model and different solubilization loci. Results indicated that the free energy change of micellar binding, delta Gb, decreases with increased steroid polarity. The simultaneous solubilization cannot be predicted by delta Gb but may be explained by differences in the solubilization mechanism.

Simultaneous solubilization of steroid hormones I: estrogens and C21 steroids.

The simultaneous solubilization of some estrogens and C21 steroids in aqueous polysorbate 40, tetradecyltrimethylammonium bromide, and sodium lauryl sulfate was studied. The less soluble estrogen estradiol was solubilized independently of the C21 steroids. The micellar solubilities of ethinyl estradiol and both corticosterone and hydrocortisone were independnet of the presence of each other while the solubility of 11alpha-hydroxyprogesterone was enhanced by ethinyl estradiol. The solubilizations of ethinyl estradiol and the two C21 steroids, progesterone and 21-hydroxyprogesterone, were dependent on each other so that a varying amount of the steroid solubilized first was precipitated by an excess of the second steroid. If saturated solutions of the two steroids were mixed, no precipitation occurred. A possible mechanism for the simultaneous solubilization of steroids and its relation to structure are discussed.