Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease.

BACKGROUND: Refractory sprue with malabsorption carries a risk of lymphoma. AIM: To examine whether a good clinical but poor histological response during a strict gluten-free diet predicts a poor outcome. METHODS: The study involved all coeliac patients who showed no histological recovery within 2 years on a strict gluten-free diet. Small intestinal biopsy and bone mineral density were investigated in 2001 and clinical features were followed up until 2005. The results were compared to those in 18 coeliac patients with a good histological recovery. RESULTS: Thirteen coeliac patients had persistent small intestinal villous atrophy despite maintaining gluten-free diet. All had demonstrated a good clinical response. Osteoporosis was found in 58% and 22% of the non-responders and responders, respectively (P = 0.04). In 2005, two of the non-responders had developed symptomatic refractory sprue, one died of lymphoma and one of carcinoid tumour, and one gastric adenocarcinoma was operated. None of the 18 controls had developed refractory sprue or malignancy. The frequency of histological non-responsive disease was 1.9%. CONCLUSIONS: Persistent villous atrophy in adult coeliac disease, even in the absence of symptoms, carries a risk of subsequent severe complications. The follow-up biopsy is important in detecting these individuals.

Pharmacokinetics and bone effects of budesonide in primary biliary cirrhosis.

BACKGROUND/AIM: To evaluate the safety of budesonide in primary biliary cirrhosis. METHODS: 77 primary biliary cirrhosis patients, with stages I-III at entry, were randomized to use either budesonide 6 mg and ursodeoxycholic acid 15 mg/kg (group A), or ursodeoxycholic acid alone (group B) daily for 3 years. In 22 patients, budesonide pharmacokinetics was determined after 3 years. Bone mass density was measured in 62 patients at baseline and 3 years; in 57 patients also liver biopsies were performed. RESULTS: At 3 years, no significant differences in the pharmacokinetics of budesonide were found between the patients with stages 0-I, II and III primary biliary cirrhosis. In group A, bone mass density in femoral neck and lumbar spine were decreased by 3.6% (P = 0.0002) and 2.8% (P = 0.003) from the baseline. In group B, the corresponding decreases were 1.9% (P = 0.029) and 0.7% (P = 0.25), but the differences between the groups were not statistically significant (P = 0.16 for femoral neck and P = 0.08 for lumbar spine). CONCLUSIONS: The plasma concentrations of budesonide do not significantly differ within stages I-III primary biliary cirrhosis patients. The combination of budesonide and ursodeoxycholic acid may decrease bone mass density in the femoral neck and lumbar spine in some primary biliary cirrhosis patients, and bone mass density is recommended to be monitored during budesonide therapy.

Ursodeoxycholic acid treatment lowers the serum level of antibodies against pyruvate dehydrogenase and influences their inhibitory capacity for the enzyme complex in patients with primary biliary cirrhosis.

A two-year randomized, double-blind, placebo-controlled clinical trial used paired serum samples from 122 patients with primary biliary cirrhosis to compare the effect of ursodeoxycholic acid and colchicine on their immune parameters. IgG antibodies to pyruvate dehydrogenase, the major autoantigen in primary biliary cirrhosis, were determined by enzyme-linked immunosorbent assay and immunoblot; enzyme inhibition assay against pyruvate dehydrogenase was used to test the changes of the functional reactivity of the serum autoantibodies. Treatment with ursodeoxycholic acid decreased both the level of IgG antibodies to pyruvate dehydrogenase (P < 0.01) and the inihibitory titer of the sera for pyruvate dehydrogenase (P < 0.01). Treatment with colchicine or placebo showed no statistically significant changes in either the antibody levels or the inhibitory titers. Ursodeoxycholic acid thus alters the immune parameters of patients with primary biliary cirrhosis. The mechanism of these changes needs further investigation.

Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21.

In inflammatory bowel diseases (IBD), certain chromosomal candidate loci have been repeatedly identified by independent studies in different populations. To investigate the contribution of the loci on chromosomes 1, 3, 7, 12, 14, and 16 to the susceptibility of IBD in Finnish population, where the predominant feature is the excess of ulcerative colitis (UC) families compared to Crohn's disease (CD) families, we carried out linkage analyses using 93 Finnish, multiply-affected IBD families. We observed nominal evidence for linkage to chromosome 3p21, consistent with earlier reports. The lod scores peaked at D3S2432, with a maximum two-point lod score of 1.68 (P=0.0027). In addition, we studied whether risk of IBD is associated with functional variants of two positional candidate genes; the chemokine receptor CCR5 gene on chromosome 3p21 and the interleukin-4 receptor alpha-subunit gene (IL4RA) on chromosome 16. We did not find any significant correlation between a 32-bp deletion variant of CCR5 or a single nucleotide change A1902G (Gln576Arg) of IL4RA, and IBD phenotypes, with the exception that in the UC group homozygosity for the G1902 allele of IL4RA was less frequent (0.019 vs 0.049, P=0.038). In conclusion, our study, carried out in a genetically homogenous population, suggests that chromosome 3 may contain a susceptibility gene for IBD.

Budesonide enema in active haemorrhagic proctitis--a controlled trial against hydrocortisone foam enema.

BACKGROUND: The aim was to compare budesonide enema, 2 mg/100 mL (Entocort) and hydrocortisone acetate foam enema, 125 mg (Colifoam) in patients with active haemorrhagic proctitis. METHODS: The trial was a controlled, randomized, investigator-blind study with two parallel groups. Endoscopy, histology and diary cards were used to assess the response to therapy. Safety was assessed by laboratory tests and adverse event recording. RESULTS: Seventy-two patients were included. Investigations were made before treatment and after 2 and 4 weeks. Both treatment groups showed statistically significant improvement in endoscopic scores but significant differences between the groups were not found. In the hydrocortisone group, plasma cortisol was significantly lowered after 4 weeks compared with budesonide. Bowel habits and quality of life variables did not differ between the treatments. The recorded adverse events were mild or moderate and may have been due to the proctitis. CONCLUSIONS: These results suggest that budesonide enema is as effective as hydrocortisone foam enema, but without the potential for side-effects associated with suppression of plasma cortisol.

Antibodies to pyruvate dehydrogenase in primary biliary cirrhosis: correlation with histology.

Antimitochondrial antibodies to pyruvate dehydrogenase are the hallmark of primary biliary cirrhosis. Their pathogenic role has not been proven, although antibodies to pyruvate dehydrogenase are bound to biliary epithelium. The aim of this study was to characterize serum IgA antibodies to pyruvate dehydrogenase and to evaluate their response to different treatment regimens. We also compared the level of antibodies with severity of histological lesions and the data of biochemical liver tests. Serum samples were collected at baseline and after 24 months from 61 primary biliary cirrhosis patients, whereas 23 patients were treated with ursodeoxycholic acid, 20 with colchicine, and 18 with placebo. ELISA was used to detect antibodies to pyruvate dehydrogenase. IgA and IgG were separated with jacalin and protein-A, respectively. Capacity of immunoglobulins to inhibit enzymatic activity was detected by spectrophotometric observation of the rate of enzyme reaction. 49 (80.3%) of the 61 patients possessed IgA antibodies to pyruvate dehydrogenase. Significant decrease in IgA antibodies was observed only in the ursodeoxycholic acid group (p<0.05). 15 of 18 IgA preparations and all 24 IgG preparations of patients' sera were inhibitory towards pyruvate dehydrogenase (mean inhibitory percent +/-SD: 42+/-33.4% and 79+/-22.4%, respectively, at a protein concentration of 100 microg/ml). The level of serum antibodies to pyruvate dehydrogenase correlated with several histological parameters (fibrosis, inflammatory infiltrate), but not with biochemical parameters. Our data reveal that IgA antibodies to pyruvate dehydrogenase inhibit enzyme function. The correlation between antibodies to pyruvate dehydrogenase and histological parameters might suggest the pathogenic role of these antibodies.

Relationship of pancreatic function and glucose tolerance to the morphology of the pancreatic ductal system as revealed by ERCP.

A series of 226 patients with suspected pancreatic disease examined with ERCP, included 130 patients with normal ductal morphology (group I), 24 with 1-2 smooth narrowings of the main duct of the pancreas (group II), 20 with ectatic small branches (group III), 22 with an irregular main duct and ectatic small branches (group IV), and 30 patients with other findings in the pancreatogram. Pancreatic exocrine function was measured in 140 patients using the secretin test. The mean value of the maximal bicarbonate concentration was significantly (p less than 0.001) lower in the patients with severe ductal changes than in those with a normal pancreatogram. In addition, the number of patients with impaired exocrine function was significantly higher in group IV than in group I. The other groups did not differ significantly. A two-hour glucose tolerance test was done on 104 patients in addition to which 19 patients had overt diabetes. The number of patients with abnormal glucose tolerance was significantly higher in group IV (60%) than in group I (27.5%). The mean blood sugar value was also higher after one hour in group IV than in group I. The patients in the other groups did not differ significantly with regard to glucose metabolism. An almost significant negative correlation was found between the maximal bicarbonate concentrations and the one-hour blood glucose values (p less than 0.05).

Clinical significance and outcome of gastric mucosal erosions: a long-term follow-up study.

Our purpose was to evaluate the long-term clinical significance of gastric erosions. A series of 117 patients with gastric erosions without peptic ulcer disease, and matched controls were studied in 1974-1979. All available subjects were reinvestigated 17 years later, including detailed clinical history and laboratory analysis. At follow-up, erosions were still more prevalent (39%; 20/50) in the erosion group than in the controls (11; 7/66). In Helicobacter pylori-positive participants, peptic ulcer or a scar was more common in the erosion group (17%; 9/52) than in controls (5%; 3/66). Overall malignancy rate was higher in controls (15%; 17/117) than in erosion group (5%; 6/117; P = .025), but no other differences were seen between the groups or related with current erosion. We conclude that a significant proportion of gastric erosions are chronic or recurrent but mostly without serious complications. However, H. pylori-positive patients with erosions have significant risk to develop a peptic ulcer.

Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial.

Ursodeoxycholic acid (UDCA) is a safe medical therapy for primary biliary cirrhosis (PBC), but its effect on liver histology remains uncertain. Budesonide is a glucocorticoid with high receptor activity and high first-pass metabolism in liver. We evaluated the combination of budesonide and UDCA on liver histology and compared this with UDCA alone in a 3-year prospective, randomized, open multicenter study. Patients with PBC (n = 77), at stages I to III, were randomized into 2 treatment arms, A (n = 41): budesonide 6 mg/d and UDCA 15 mg/kg/d and B (n = 36): UDCA 15 mg/kg/d. Liver histology was assessed at the beginning and at the end of the study. Liver function tests and glucose and cortisol values were determined every 4 months. Paired liver biopsy specimens were available from 69 patients (A = 37 and B = 32). Stage improved 22% in group A but deteriorated 20% in group B (P = .009). Fibrosis decreased 25% in group A but increased 70% in group B (P = .0009). S-PIIINP decreased significantly in group A. Inflammation decreased in both groups, 34% in group A (P = .02), but only 10% in group B (P = NS). Serum liver enzymes decreased significantly in both treatment arms. Bilirubin values rose in group B but stayed stable in group A (A/B P = .002). A mild systemic glucocorticoid effect from budesonide was evident after 2 years. In conclusion, budesonide combined with UDCA improved liver histology, whereas the effect of UDCA alone was mainly on laboratory values. Studies with longer follow-up using a combination of budesonide and UDCA are warranted to confirm safety and effects.

Occurrence of gastric mucosal erosions in association with other upper gastrointestinal diseases, especially peptic ulcer disease, as revealed by elective gastroscopy.

In an elective gastroscopic series of 3837 patients, gastric mucosal erosions were observed in 404 (10.5%) patients, 215 (5.6%) having only erosions without other endoscopic findings in the upper gastrointestinal tract. The male to female ratio was 1.3:1. The number of patients with erosions was highest in the age groups 41-60 years. The patients with erosions were younger than those with peptic ulcer studied during same period. The erosions were located in the distal part of stomach only in 86% of patients. Erosions were observed in 3.5% of patients with stomach resected for peptic ulcer. The positive association with active duodenal ulcer was significant, but there was a negative correlation to gastric cancer, with an almost significant difference compared with patients without gastric erosions randomly selected from the same elective gastroscopic series. The seasonal variation of occurrence resembled more that of gastric than duodenal ulcer.