J. Lehtola

A placebo-controlled trial of primary biliary cirrhosis treatment with colchicine and ursodeoxycholic acid

BACKGROUND/AIMS Ursodeoxycholic acid (UDCA) and colchicine have beneficial effects in primary biliary cirrhosis (PBC). The efficacy of colchicine and UDCA in PBC was compared in a 2-year placebo-controlled study (n = 90). METHODS Clinical events, laboratory test results, and liver histology were recorded at the beginning and end of the trial. RESULTS There were significantly fewer dropouts for hepatic reasons with UDCA than with placebo. Pruritus was reduced by both active drugs. Colchicine improved liver function test results only modestly, whereas UDCA significantly decreased the serum activities of aminotransferases, alkaline phosphatase, and gamma-glutamyltransferase compared with colchicine and placebo. Serum total bilirubin levels were decreased only by UDCA. Both colchicine and UDCA reduced serum cholesterol levels, and UDCA also reduced high-density lipoprotein cholesterol levels. Furthermore, UDCA reduced the serum levels of immunoglobulin (Ig) M and IgG, and colchicine reduced IgG levels compared with placebo. The elevated serum level of aminoterminal propeptide of type III procollagen remained unchanged by colchicine or UDCA, whereas the serum level of carboxyterminal propeptide of type I procollagen was significantly decreased by UDCA. UDCA significantly decreased ductular proliferation compared with colchicine or placebo. CONCLUSIONS These data suggest that UDCA frequently is superior to colchicine and especially to placebo in the treatment of PBC.

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 cross-sectionally. 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 Crohns 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.

Smoking is a risk factor for osteoporosis in women with inflammatory bowel disease.

BACKGROUND Some patients with inflammatory bowel disease have reduced bone mineral density, but the risk factors for osteoporosis in these patients are unclear. METHODS To evaluate the effect of smoking and other lifestyle factors on bone mineral density in patients with inflammatory bowel disease, we studied 67 patients with ulcerative colitis, 78 with Crohns disease, 7 with indeterminate colitis, and 73 healthy control subjects. Bone mineral density of the lumbar spine and the proximal femur was measured, using dual-energy X-ray absorptiometry. Measures of smoking and other lifestyle factors were assessed in an interview. RESULTS The female ex- or current smokers with inflammatory bowel disease (n = 38) had lower age- and sex-adjusted Z-scores of bone mineral density than the female patients who had never smoked (n = 34) (Z-scores in the lumbar spine, -0.277 (1.283) (mean (standard deviation)) and 0.487 (1.056), respectively; p = 0.008; and in the femoral neck, -0.626 (1.055) and -0.013 (1.019); p = 0.015). These differences were not explained by the type or treatment of the disease, the menstrual history, or the use of estrogen preparations. In male patients no differences in bone mineral density were found between ex- or current smokers and non-smokers. Coffee drinking and alcohol consumption were not associated with bone mineral density in these patients. CONCLUSIONS Smoking is associated with low bone mineral density in women with inflammatory bowel disease. This association is not related to the body mass index, the medical treatment, or the type of disease.

Collagenous colitis and Yersinia enterocolitica infection

Collagenous colitis is a rare clinical andpathological entity characterized by watery diarrhea anddeposition of collagen beneath the surface epithelium ofthe colon. Its etiology is unknown. We present a careful retrospective clinicopathologicalanalysis of six patients with collagenous colitisdiagnosed at our hospital during a three-year period.Three of the patients had had a Yersinia enterocolitica infection, detected by stool culture andelevated serum antibody titers, preceding the diagnosisof collagenous colitis. Four patients had duodenalvillous atrophy, which in two patients was refractory to a gluten-free diet. We propose that Yersiniaenterocolitica infection may be a triggering factor forthe development of collagenous colitis in some cases.Duodenal villous atrophy not responding to gluten withdrawal is common in association withcollagenous colitis.

Clinical characteristics of collagenous and lymphocytic colitis

Background: Microscopic colitides (MC), collagenous colitis (CC) and lymphocytic colitis (LC) share clinical features, but their mutual relationship is unclear, and clinical comparative studies are rare. We aimed to examine the clinical features in CC and LC by focusing on concomitant diseases. Methods: Patients with MC (30 with CC, 54 with LC) were identified in the pathology databases and by reviewing biopsies. Controls included 84 age‐ and sex‐matched persons. The clinical data collected from patient records were prospectively completed by interviews. Results: The female:male ratio was 2:1 in CC and 5.75:1 in LC. Mean age at diagnosis was 53 in CC and 55.4 years in LC. There were no differences in the pattern of symptoms. Concomitant autoimmune diseases were more common in CC (53.3%) than in LC (25.9%; P = 0.017). Celiac disease was common in both CC (20%) and LC (14.8%). Bronchial asthma was associated with LC (25.9%), but not with CC (6.7%; P = 0.042). Colon diverticulosis was rare in MC (16%) compared with the controls (39%; P = 0.001). Hypolactasia was common in MC (45%; 76% in CC, 54% in LC) compared to its prevalence in the Finnish general population (17%). Conclusions: CC and LC are largely similar clinically, but the differences in the occurrence of autoimmune conditions and bronchial asthma suggest that they differ in immunopathogenesis. MC is associated with reduced lactose tolerance and shows a negative association with diverticular disease, possibly related to the small intestinal pathology and abnormal stool consistency.

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.

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.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.

Human leucocyte antigen and TNFα polymorphism association in microscopic colitis

Objectives Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNF&agr; gene polymorphism (−308) associated with susceptibility to several autoimmune diseases was studied. Methods Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNF&agr;(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNF&agr; study. Results HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). Conclusion Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.

Dietary calcium intake and its relation to bone mineral density in patients with inflammatory bowel disease

Objectives. To investigate calcium intake and its association with bone mineral density (BMD) and the type and extent of the disease in patients with inflammatory bowel disease (IBD).

Campylobacter-Like Organisms and Gastritis: Histopathology, Bile Reflux, and Gastric Fluid Composition

We studied a prospective series of 107 randomly chosen dyspepsia patients without gastric ulcer for the association of spiral Campylobacter-like organisms (CLO) with features of antral and fundal gastritis and duodenogastric reflux. CLO were observed in 38% of the patients. The scores for all classes of inflammatory cells in both antral and body mucosa were significantly higher in the CLO-positive patients than in the CLO-negative ones (p less than 0.001), and foveolar hyperplasia was also associated with CLO (p less than 0.05). Metaplasia and glandular atrophy in the antral mucosa were significantly commoner in the CLO-positive group (p less than 0.05 and p less than 0.01, respectively). The body gastritis score correlated significantly with age in the CLO-negative patients (R = 0.33, p less than 0.01) but not in the CLO-positive ones. There were no significant differences between the groups with regard to duodenogastric reflux or intragastric pH. The results confirm that CLO are associated with gastritis, most notably superficial gastritis in the body and atrophic gastritis in the antrum, but their aetiological significance remains to be proved.