Abstract: AIM: To evaluate the predictive value of tissue transglutaminase (tTG) antibodies for villous atrophy in adult and pediatric populations to determine if duodenal biopsy can be avoided. METHODS: A total of 324 patients with celiac disease (CD; 97 children and 227 adults) were recruited prospectively at two tertiary centers. Human IgA class anti-tTG antibody measurement and upper gastrointestinal endoscopy were performed at diagnosis. A second biopsy was performed in 40 asymptomatic adults on a gluten-free diet (GFD) and with normal tTG levels. RESULTS: Adults showed less severe histopathology (26% vs 63%, P < 0.0001) and lower tTG antibody titers than children. Levels of tTG antibody correlated with Marsh type in both populations (r = 0.661, P < 0.0001). Multiple logistic regression revealed that only tTG antibody was an independent predictor for Marsh type 3 lesions, but clinical presentation type and age were not. A cut-off point of 30 U tTG antibody yielded the highest area under the receiver operating characteristic curve (0.854). Based on the predictive value of this cut-off point, up to 95% of children and 53% of adults would be correctly diagnosed without biopsy. Despite GFDs and decreased tTG antibody levels, 25% of the adults did not recover from villous atrophy during the second year after diagnosis. CONCLUSION: Strongly positive tTG antibody titers might be sufficient for CD diagnosis in children. However, duodenal biopsy cannot be avoided in adults because disease presentation and monitoring are different.
Abstract: OBJECTIVES: To describe the frequency and the clinical and laboratory characteristics of relapsing acute pancreatitis (AP) associated with gluten enteropathy (GE). PATIENTS AND METHODS: We prospectively examined all acute pancreatitis cases admitted to our Department in 2006. We recorded a total of 185 patients. With recurring forms, 40 (22%) in all, we used a clinical-lab protocol including serologic and genetic markers, and duodenal biopsy to rule out GE. RESULTS: A total of 34 patients (18%) met clinical-biological criteria for GE (group1), and were compared to the remaining non-GE AP cases (n=161) (group2). Mean age in the GE group was 54 +/- 25 years, slightly younger than group 2 (61 +/- 14) (NS). There was a mild predominance of women (50%) in group 1 versus group 2 (38.5%) (NS). Seven patients in group 1 (20%) had severe AP, as compared to 27 (17%) in group 2 (NS). The presence of cholelithiasis in group 1 involved 6 cases (18%), which was significantly lower than in group 2--72 cases (45%) (p < 0.05). Four patients with GE developed pseudocysts (12%) versus 13 (8%) in group 2 (NS). Tissue transglutaminase (tTG) was elevated only in 3 patients (9%). Nine patients (34%) were DQ2 (+) and 4 (12%) DQ8 (+); the rest (54%) were all negative for both markers. From an endoscopic perspective there was diffuse duodenitis in 32 patients (95%). Duodenal biopsies revealed villous atrophy (Marsh 3) in 2 patients (6%); submucosal inflammatory infiltration (Marsh 2) in 10 (29.4%); increased intraepithelial lymphocytes (Marsh 1) in 8 cases (23.5%), and normal mucosa (Marsh 0) in 14 patients (41.2%). Response to GFD after 1 year was excellent in 30 patients (88%). CONCLUSIONS: Relapsing AP with GE represents a relatively common association that is indistinguishable from other APs from a clinical-evolutive standpoint, except for a lower presence of cholelithiasis (p < 0.05). A specific diagnostic protocol is much needed in the identification of these patients since GFD is the only effective therapy to prevent new AP events from developing.
Abstract: AIM: To evaluate the factors involved in the impairment of health-related quality of life (HRQOL) in patients with celiac disease. METHODS: A multicenter, cross-sectional prospective study was performed in patients with celiac disease who completed two HRQOL questionnaires: the gastrointestinal quality of life index (GIQLI) and the EuroQol-5D (EQ). RESULTS: Three hundred and forty patients (163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet) were included. The GIQLI score was significantly better in patients on a gluten-free diet (GFD) than in non-treated patients on their usual diet, both in terms of the overall score (3.3 vs 2.7, respectively; P < 0.001), as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients (0.93 vs 0.72 P < 0.001 and 80 vs 70 P < 0.001, respectively). Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION: In untreated celiac disease, the most important factors that influence patient perception of health are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.
Abstract: The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R alpha mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15R alpha mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15R alpha expression was only triggered in non-CD controls (P = 0.0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFN gamma (P = 0.0313, P = 0.0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.
Abstract: INTRODUCTION: celiac disease (CD) is an autoimmune condition that is triggered by the ingestion of gluten, a substance present in most cereals, and that affects genetically predisposed individuals. As a result, this condition is clearly familial, and mainly associated with HLA class II markers. OBJECTIVES: in this work we set out to analyze the prevalence of CD in an extensive family based on an index subject who had already died from this disease a few years ago, where CD had been complicated by the development of a small-bowel malignancy, namely an adenocarcinoma. METHODS: nineteen members were studied. They all were subjected to a diagnostic protocol including a detailed medical history, hemogram, coagulation tests, and blood biochemistry (including liver function tests, serum iron metabolism, circulating folic acid and vitamin B12 levels, thyroid function tests, tissue transglutaminase measurement, and genetic markers (DQ2 and DQ8). Suspect cases underwent gastroscopy plus multiple duodenal biopsy for confirmation. RESULTS: overall we encountered CD in 9/19 studied members, which represents 47.4% with the following distribution according to degree of kinship -four of seven siblings (57%); one of three children (33.3%); three of eight nephews and nieces (37.5%), and the only grandnephew, who was 9 years old. CONCLUSIONS: from all this it may be seen that family studies are needed every time a patient is diagnosed with celiac disease; these studies should include both first- and second-degree relatives, given the high prevalence encountered and the fact that these tests are relatively straighforward to perform.
Abstract: BACKGROUND: the association between the three common CARD15 gene mutations (R702W, G908R, L1007fs) and the genetic susceptibility to Crohn s disease (CD) have been confirmed by several studies, with some differences found, in relation to geographic areas and ethnic groups. OBJECTIVES: To analyze the prevalence of CARD15 gen and its polymorphisms in patients with CD in Asturias and its possible correlation with the different genotypes of the disease. METHODS: a total of 216 CD patients recruited from Asturias (North of Spain) and 86 ethnically matched healthy controls, were typed using Hybprobes on a LightCycler instrument for CARD15 mutations. Patients were subdivided according to Vienna classification. We have studied the frequency of these mutations in the different subgroups of CD patients and analyzed its contribution to the disease clinical characteristics and progression. RESULTS: carrier frequencies for CARD15 mutations in our CD patients were similar to controls (17.8 vs. 17.4%) respectively (NS). CD patients exhibited frequencies of 8.8, 3.0 and 6.0% for the R702, G908R and L1007fs polymorphisms respectively, whereas our control population had allele frequencies of 11.6, 2.3 and 3.5% for the three mutations respectively (NS). We did not find any relationship between CARD15 mutations and the different phenotypes of Crohn s disease, according to Vienna classification. CONCLUSIONS: in our CD population, other factors (i.e. environmental), in addition to genetics, must be mainly involved in the development of the disease.
Abstract: BACKGROUND: Infliximab induces remission and improves the health-related quality of life (HRQOL) of patients with refractory or fistulous Crohn's disease (CD). However, little information is available as to whether its effect on HRQOL is sustained over time. The objective was to measure the HRQOL of CD patients in long-term clinical remission. METHODS: Prospective, observational study was undertaken in patients with CD in infliximab-induced clinical remission (Harvey index <3) for at least 6 months, and receiving long-term infliximab and azathioprine maintenance therapy. Patients were followed for 4 years or until clinical relapse (Harvey index >3). HRQOL was assessed annually using the validated Spanish version of the disease-specific 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) and the EuroQol-5D. RESULTS: Forty-nine patients with CD in stable clinical remission were included at baseline. At 12 months, n = 42 patients remained in remission, at 24 months n = 32 patients, at 36 months n = 13, and in the last visit at 48 months 6 patients remained in clinical remission. The overall score on the IBDQ-36 remained unchanged in patients with stable, inactive CD (median overall score of 6.1 at baseline and 6.5 at 4 years). Scores on all 5 dimensions of the IBDQ-36 remained unchanged over the study period in stable patients. Patients in remission scored highly on the preference value ratings of the EuroQol-5D (scores of 1.0) and remained unchanged in patients who remained in remission. CONCLUSIONS: Sustained clinical remission of CD achieved with maintenance treatment maintains HRQOL over long-term follow-up.
Abstract: OBJECTIVES: To examine the feasibility and to perform a cost benefit analysis of a 5-sample pooling strategy using an enzyme immunoassay (EIA) for the screening of hepatitis B surface antigen (HBsAg). MATERIAL AND METHODS: To assess the sensitivity and specificity of the pooling method, each of the 40 positive sera (from weak to intensely HBsAg-positive) and 250 negative sera were tested in a pool with 4 HBsAg-negative sera. The limit of detection for HBsAg/ad and HBsAg/ay was evaluated using sera from a panel of purified subtypes. A study under real conditions was conducted using pools from 340 pregnant women. RESULTS: The sensitivity and specificity of this technique were 100%. The correlation coefficient among the sample/cutoff ratios of 40 samples studied in single and in pooled conditions was 0.792 (p < 0.005). The pooling method has lower levels of detection for HBsAg/ad and HBsAg/ay at 0.20 ng/mL and 0.12 ng/mL, and the single method at 0.34 ng/mL and 0.29 ng/mL, respectively. The pooling method loses no sensitivity for values up to 100 IU/L of anti-HBs in the four sera mixed with a positive serum. The cost-benefit analysis showed that the pooling method could save from 30% up to 75% of the cost of HBsAg determination, according to whether seroprevalences were 10% or 1%, respectively. CONCLUSIONS: The pooled HBsAg EIA yielded no worse than the single EIA test, and was a cost-effective and valid strategy in areas with a high, medium or low prevalence.
Abstract: AIM: To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS: A 15 year-trend (1990 to 2004) in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS: Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies (7.6%); an increase in the use of such was observed over the study period (1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004). Celiac disease was diagnosed in 22 patients (2.2%), this being more frequent in women than in men (3% and 1% respectively). Fourteen out of 514 (2.7%) patients with anaemia, 12 out of 141 (8.5%) with chronic diarrhoea and 8 out of 42 (19%) with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION: Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.
Abstract: We discuss the case of a 17-year-old male who at the age of 7 was diagnosed with celiac disease (CD) together with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). The patient was treated with gluten-free diet and immunosuppressive drugs (azathioprine), and currently remains asymptomatic. The patient's younger, 12-year-old sister was diagnosed with CD when she was 1.5 years old, and at 7 years she developed type-I diabetes mellitus, which was difficult to control. A family study was made, and both parents were found to be affected with silent CD. All were DQ2 (+). In relation to the case and family study, we provide a series of comments related to CD and its complications.
Abstract: AIM: Celiac disease (CD) is an enteropathic disorder very prevalent in Saharawi people. Our aim was to investigate the diagnostic accuracy of six human tissue transglutaminase (tTG) based ELISA tests in Saharawi CD patients. METHODS: Fifty-two CD patients and 23 controls were selected from the Saharawi refugee camps in Tinduf. CD patients were divided into two groups according to their anti-endomysium (EmA) status: 41 EmA positive and 11 EmA negative. Sera from patients and controls were tested for human tTG using six commercial ELISA kits. We used receiver operating characteristics (ROC) curves and areas under the curve to compare the diagnostic accuracies of the six assays. RESULTS: In general, there are differences in the sensitivity and specificity of the human tTG ELISA assays used. Diagnostic accuracy of tests was significantly improved by adjusting the cut-off thresholds according to ROC plot analysis; the correction of the cut-off with the employment of the ROC curve analysis modifies the decision limit in more than 50% in five of the six kits evaluated. CONCLUSION: Some of the human tTG ELISAs used in this study have a diagnostic accuracy similar to EmA determination for diagnosis of CD in Saharawi people. However, it is necessary to select the assay with a higher sensitivity and specificity, and recalculate the cut-off threshold using samples from the referral population.
Abstract: We performed a family study to evaluate a total of 34 extended family members (8 siblings, 23 children and nephews, and 3 grandchildren) of an adult patient with celiac disease (CD), a 58- year-old male with severe neurologic involvement manifested as myoclonias. We found 3 other members affected with CD (a 44-year old sister, a 39-year old niece, and a 26-year old nephew). Two of them were completely asymptomatic and all had hypertransaminasemia. All exhibited a villous atrophy pattern of the duodenal mucosa (1 mild, 1 moderate, 1 severe). Overall family involvement was 11.8% (4/14). We wish to emphasize the need to perform extended family studies when diagnosing a case of CD, since risk is not restricted to only first-degree relatives.
Abstract: OBJECTIVE: to assess the incidence of inflammatory bowel disease in Oviedo (Northern Spain), and to describe the clinical features of new patients. PATIENTS AND METHODS: a prospective population-based study was made at the Health Area IV, Principality of Asturias (Oviedo, 312,324 inhabitants). All new diagnosed patients with inflammatory bowel disease were registered over a 2-year period. RESULTS: a total of 85 patients were included, 47 of these with ulcerative colitis (UC), 37 with Crohńs disease (CD), and 1 with undetermined colitis. The overall adjusted incidence rate of UC and CD per 105 inhabitants between 15-64 years was 9.1 (95% CI: 5-13.1) and 7.5 (95% CI: 3.8-11.2), respectively. The global male/female ratio was 0.9, without significant differences between both diseases. CD patients were younger than those with UC (33 +/- 15 years vs 45 +/- 20 years; p < 0.05). Mostly, CD patients were diagnosed at an age younger than 35 years (65%), while UC patients were diagnosed at an age between 25 and 64 years (81%). Disease extension in UC was proctitis in 11%, left-side colitis in 53% and extensive colitis in 36%. With respect to CD, the ileo-colonic form predominated (49%), followed by the ileal (40%) and colonic (11%) forms; an inflammatory, stenotic and fistulous pattern was seen in 54, 22 and 24% of patients, respectively. CONCLUSIONS: in our area, the incidence of CD is similar to that in other Northern European countries, while UC has a lower incidence. CD mainly affects young people, while UC predominates in middle-aged patients. At diagnosis, UC is predominantly localized, the ileo-colonic form and an inflammatory pattern being most frequent in CD patients.
Abstract: AIMS: The epidemiologic analysis inflammatory bowel disease (IBD) is a powerful research tool to assess the contribution of environmental factors to its etiology. IBD has been reported to have varying frequencies in different parts of the world, and there seem to be significant differences in the disease pattern and clinical course. The aim of the present study was to assess the disease pattern of IBD in Asturias (Spain). PATIENTS AND METHODS: A descriptive epidemiological population based study, retrospective (1954-1993) and prospective (1994-97), was performed to study 1018 patients found, bigger than 14 years, to have IBD, in five areas of Asturias (Spain) (461.965 inhabitants). RESULTS: During the period of time studied, we diagnosed 1018 IBD [565 ulcerative colitis (55.5%), 415 (40.8%) Crohn's disease and 38(3.7%) indeterminate colitis], with 482 females (47.2%), 536 males (52.8%), and male/female: 1.11. Age at diagnosis were 39.49 +/- 1.08 (95% CI : 38.41 +/- 40.57); (UC: 43.95 +/- 1.47; CD: 33.53 +/- 1.51; IC: 38.26 +/- 5.14. p = 0.000. Age at onset previously at diagnosis for UC: 42.84 +/- 1.34; CD: 30.68 +/- 1.40; IC: 36.74 +/- 4.86 (p = 0.000). Diagnosis criteria: UC: syntomatic 97.34% (p = ns), endoscopy 96.63% (p = 0.000 pathology 90.26% (p = 0.000). CD: radiology 83.61% (p =0.000). Study level in CD: 57.57 (p = 0.0005). Family history: 8.4%. The most frequent involvement at diagnosis of UC was proctitis only, in 13.6%, 269% rectum and sigmoid 26% let colitis, 20% pancolitis, and in CD colon only, in 16.7%, 30.3% terminal ileum, 41.3% ileo-colon of the patients. This also helps to explain the differences in severity, need for surgery, and survival noted between community based studies. CONCLUSIONS: We highlight the uniformity of distribution of the inflammatory bowel disease in relation to types and sex. The high frequency of familial Crohn's disease suggests a genetic predisposition. Highlighting a bigger morbilidad for the Crohn's Disease reflected in the surgical requirements, but however with smaller mortality that in ulcerative colitis.
Abstract: AIMS: To know and to compare Inflammatory Bowel Disease (IBD) Incidence and Prevalence rates in in five areas of Asturias (Spain). We conducted a prospective epidemiologic study of IBD in the Province of Liege (1 million inhabitants). PATIENT AND METHODS: We conducted a descriptive, populational, collaborative epidemiologic study, retrospective between 1954 and 1993 and prospective between 1994 and 1997. All patients diagnosed according to a standard protocol for case ascertainment and definition of IBD, aged 14 years or more are included, in five areas of Asturias (Spain) (461,965 inhabitants). RESULTS: For the period 1954 to 1997, 1018 IBD have been diagnosed [565 ulcerative colitis (UC) (55.5%), 415 Crohn's disease (CD) (40.8%) and 38 undefined IBD (IC) (3.7%)]; [482 women (47.2%), 536 males (52.8%)]. In the 4 year-prospective period, 306 cases were collected: 176 UC (57.51%), 110 CD (35.94) and 20 IC (6.53%); UC/CD: 1.6. Without appreciable and significant differences between Frequency of illness groups and sexes. IBD incidence rate (per 100,000 per year) (1954-97) is 5.12 (95% CI = 3.05-7.18) (UC: 2.84; CD: 2.08; IC: 0.19; UC/CD 1.36). In the 4 years- prospective study, IBD incidence rate is 16.55 (95% CI = 12.84-20.25), (UC: 9.52; CD: 5.95; IC: 1.08; UC/CD: 1.6). IBD prevalence rate in 1997 is 205.21 (95% CI = 182.14-227.29), (UC: 109.96; CD: 87.45; IC: 7.79). Comparisons have settled down among the studied areas, without finding differences statistically significant. CONCLUSIONS: Inflammatory Bowel Disease incidence and prevalence rates of in our region are homogeneous between the cities investigated and superior than those historically reported in Spanish studies. These results were similar to those observed in European studies.
Abstract: BACKGROUND AND AIMS: The natural history of functional dyspepsia is not well known. We prospectively assess the quality of life and severity of symptoms in a group of Spanish patients with functional dyspepsia. PATIENTS AND METHODS: One hundred and twelve consecutive patients with functional dyspepsia, according to Rome II criteria, were prospectively followed up for 1 year. All patients completed symptom (Dyspepsia Questionnaire and the Gastrointestinal Symptoms Rating Scale) and quality of life [the Psychological General Well-Being (PGWB) Index and the General Health Questionnaire (GHQ)] questionnaires every 3 months. Only free antacid consumption was permitted during the study period. RESULTS: The group was made up of 81 women and 31 men with a mean age of 45 +/- 17 years; 66% of patients were infected with Helicobacter pylori, and ulcer-like dyspepsia (53%) was the predominant subgroup. At baseline, quality of life scores were low (PGWB, 87.1 +/- 17.6 and GHQ, 20.6 +/- 11.8), but these values gradually improved during the year of follow-up (PGWB, 107.7 +/- 1.1 and GHQ, 8.9 +/- 0.4). Digestive symptoms also decreased. In the multivariate analysis, the anxiety score on the PGWB index (Wald, 5.2; P = 0.02) and smoking status (Wald, 4.3; P = 0.04) were predictors of end quality of life. At baseline, patients with a high level of anxiety had a very reduced quality of life, although their symptom scores were similar to other patients. CONCLUSION: Quality of life is reduced in patients with functional dyspepsia. Some improvement in quality of life together with a decrease in the severity of symptom scores was seen during the 1 year of follow-up. We believe that both the reassurance of negative endoscopy and the scheduling of visits to the doctor favourably influence the quality of life.
Abstract: We selected 38 consecutive celiac disease (CD) patients (from a group of 316 consecutive CD patients) and 91 healthy blood donors, all of whom were HLA-DQ2 (DQA1*0501/DQB1*0201) negative, and investigated the presence of the classically associated alleles HLA-DQ8 and HLA-DRB4. We also studied the distribution of MICA transmembrane alleles in the two clinical forms of the disease. For this reason, these 38 DQ2-negative patients were subdivided into two groups: 18 typical CD patients and 20 atypical CD patients. No differences were found in the distribution of the DRB4 allele between DQ2-negative patients and controls. The HLA-DQ8 heterodimer (DQA1*03xx/DQB1*0302) was increased in CD patients (29%) compared with controls (10%), but no statistical differences were found. No differences were observed in the frequency of these alleles between either group of CD DQ2-negative patients. MICA-A5.1 was increased in atypical CD patients when compared with the typical forms of disease ( P(c)=0.03) and with healthy controls (P(c)=0.002). No other MICA allele was found to be significantly increased in the groups under study. The presence of MICA-A5.1 in atypical CD DQ2-negative patients may indicate a possible role of this allele in the development of CD.
Abstract: BACKGROUND AND AIMS: Coeliac disease (CD) is an enteropathic disorder characterised by a strong association with major histocompatibility complex (MHC) heterodimer HLA-DQ2. It has been suggested that other HLA class I genes in combination with DQ may also contribute to CD susceptibility. The aim of this study was to investigate whether other candidate genes modify the risk of developing different clinical forms of CD. PATIENTS AND METHODS: We studied 133 Spanish coeliac patients, divided according to their clinical presentation into typical and atypical groups, and 116 healthy controls. All were typed by polymerase chain reaction-sequence specific primers (PCR-SSP) at HLA-B, DRB1, DQA1, and DQB1 loci and for exon 5 of the MHC class I chain related gene A (MICA). RESULTS: No differences were found in the frequency of the DQA1*0501/DQB1*0201 heterodimer in either group. The risk of typical CD was significantly associated with the DR7/DQ2 haplotype (p(c)=0.02, odds ratio (OR)=3.4, ethiological fraction (EF)=0.4). Extended haplotype (EH) 8.1 (B8/DR3/DQ2) was found to be overrepresented in the atypical form compared with the typical form (p(c)=0.001, OR=4.19, EF=0.56). The trinucleotide repeat polymorphism MICA-A5.1 was found to be increased in the atypical group of patients compared with the typical group (p(c)=0.00006, OR=8.63, EF=0.81). This association was independent of linkage disequilibrium with EH8.1 as this was also found to be increased in EH8.1 negative atypical patients compared with the typical group (p(c)=0.004, OR=6.66, EF=0.56). CONCLUSIONS: Our results showed that the risk of developing typical forms of CD was associated with DR7/DQ2 haplotype, and the presence of B8/DR3/DQ2 was significantly increased in atypical patients. In these, the MICA-A5.1 allele confers an additive effect to the DR3/DQ2 haplotype that may modulate the development of CD.
Abstract: OBJECTIVES: To estimate the prevalence of hepatitis C in a population of northern Spain and describe (i) the risk factors associated with infection and (ii) the distribution of genotypes. DESIGN: Randomized cross-sectional study. METHODS: A random sample of 1,170 people participated in the study. Sociodemographic data were obtained. Antibodies against hepatitis C virus (anti-HCV) and hepatitis C virus (HCV) genotypes were determined. RESULTS: Nineteen of 1,170 (1.6%) subjects were anti-HCV positive (95% CI 1.0-2.6%). In 12 cases (63%), viraemia was present, and the predominant genotype was 1 b (80%). Anti-HCV positive subjects were older than anti-HCV negative subjects (55.8 +/- 15.3 v. 44.8 +/- 20.9; P = 0.02). Two peaks of maximum frequency were found (in the fourth decade and in those over 60 years). Parenteral drug addiction predominates among those of the fourth decade, while transfusion and surgery predominate in people over 60 years. Three (16%) subjects knew they were carriers of HCV. Only three variables remained significant in the multivariate model (illegal drug use, P< 0.0001; previous hepatitis, P< 0.0001; and age, P< 0.02). CONCLUSIONS: Our study emphasizes the need to develop health policies that can cope with the foreseeable increases in the problems associated with HCV infection in the near future.
Abstract: We present the case of dual adult celiac disease and liver disease with portal hypertension (esophageal varices); a percutaneous liver biopsy was compatible with nonspecific reactive hepatitis. Clinically, celiac disease was characterised by poor response to a gluten-free diet, with the development of a biochemical cholestasis and marked malnutrition. Our patient died of cerebral hemorrhage, at the age of 50 years, without associated risk factors. The necropsy demonstrated the existence of a nodular regenerative hyperplasia of the liver, splenic atrophy, gelatinous transformation of the bone marrow, and lymphocytic colitis. We discuss the different types of liver disorders associated with celiac disease and the possible relation between nodular regenerative hyperplasia and celiac disease, based on immunologic mechanisms.
Abstract: The aim of this study was to define the pattern of neopterin and ADA isoenzymes in liver cirrhosis. A total of 117 patients with liver cirrhosis were included. Serum levels of ADA were assayed in the presence and absence of a specific inhibitor for ADA1. Serum neopterin was measured using a competitive enzyme-linked immunosorbent assay. The grade of liver insufficiency was assessed according to the Child-Pugh classification and the monoethylglycinexylidide test. Serum ADA, ADA1, ADA2 and neopterin were higher in cirrhotic patients than in control subjects. A stepwise increase in serum ADA level was observed with increasing severity of liver cirrhosis. The probability of ADA2 being greater than the mean was approximately 2.5 times higher (2.48, CI 95%: 1.36-4.52) in patients with liver cirrhosis due to hepatitis C virus (HCV) infection than in those patients with cirrhosis of a different etiology. No correlation was found between ADA2 and neopterin. Our data show that liver insufficiency and HCV infection increase the serum levels of ADA and its major isoenzyme ADA2. Furthermore, ADA isoenzyme determination adds no value to total ADA value. The absence of a correlation between ADA2 and neopterin suggests that different physiologic processes are involved in their increase.
Abstract: BACKGROUND: Coeliac disease (CD) is common in Western countries. In Spain, however, no studies exist on its prevalence. The best method for serologic screening is also unknown. METHODS: We determined the IgA and IgG antigliadin antibodies (AGA) and IgA antiendomysium antibodies (AEA) in a sample of 1170 randomly selected subjects from a health area in northern Spain. The prevalence of CD was calculated with a two-step serologic screening method (first IgA and IgG AGA and then AEA in those positive for AGA) or with only one step with AEA determination. Diagnosis was confirmed by small-intestinal biopsy. RESULTS: When using a two-step strategy, we found 174 (15%) subjects with AGA. Only one of these was confirmed by means of AEA (prevalence of CD = 0.9/1000). Two subjects were found to be positive when a one-step strategy was used (prevalence of CD = 1.7/1000). This yielded an economic saving of 19% with regard to the use of a two-step strategy. One new case of CD in a seronegative subject was diagnosed during the study (real prevalence of CD = 2.6/1000; 95% confidence interval = 0.7-8.2). CONCLUSIONS: The prevalence of CD in Northern Spain is 2.6/1000 (1:389). One-step serologic screening (AEA) is both more economical and more sensitive than the two-step procedure (first AGA and then AEA if AGA is positive).
Abstract: Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.
Abstract: To discover whether tamoxifen is able to extend the survival of patients with advanced hepatocellular carcinoma, we included 80 patients with cirrhosis and advanced hepatocellular carcinoma in a multicenter, double-blind, placebo-controlled trial in order to analyze the influence of treatment with tamoxifen on survival. The patients were randomized to receive tamoxifen, 40 mg/day (group 1), or placebo (group 2). Both groups were similar in age, sex, etiology of cirrhosis, biochemical, hematologic and hormonal parameters, morphology of the tumor (nodular vs multinodular or massive), Child-Pugh's score, and Okuda's stage. The 1-year survival rate was similar in both groups (30% in group 1 vs 37.8% in group 2; p = 0.31). Tamoxifen treatment was well tolerated by the patients. We conclude that tamoxifen does not extend the survival of patients with cirrhosis and advanced hepatocellular carcinoma.
Abstract: BACKGROUND: Helicobacter pylori is a worldwide infection, and it is estimated that approximately 50% of the general population is affected. However, its distribution varies considerably between developed and developing countries. AIMS: in the present study we report the results of an epidemiological investigation of the prevalence of H. pylori infection in the general population in Asturias (Northern Spain), in order to describe the current state of this infection in our region, and obtain figures for comparison with the results obtained in different communities of Spain and other countries. EXPERIMENTAL DESIGN: a descriptive transversal, epidemiological study, based on the serological determination of the IgG antibodies against H. pylori was carried out in the general population of a randomly selected sample of subjects without previous gastroduodenal antecedents. PARTICIPANTS: we analyzed 480 serum samples obtained from the general population of Asturias. These were divided into decades according to the age pyramid and tested for the presence of antibodies against H. pylori with a commercially available latex agglutination technique (Pyloriset). RESULTS: the global prevalence of H. pylori infection in our study was 226/480 (49.2%), and was slightly higher in women (50.6%) compared to men (47.6%). No significant differences were found between sexes (p = 0.51). In the first decade mean prevalence was 13.6%. In the second this figure was 25.4%, and it increased steadily to a maximum in the sixth decade of 76.4%. Thereafter, the prevalence decreased to 66.6% in persons over 80 years of age. CONCLUSIONS: we found a high prevalence approximately 50% of H. pylori infection in the general population of Asturias, as in other epidemiological studies in Spain and other European countries. The distribution according to age shows a clear tendency to increase, from childhood to adolescence and adult life (50-60 years), when prevalence is highest (76%). From this decade onwards it begins to decrease, showing a clear cohort effect with a pattern intermediate between that of developed and developing countries.
Abstract: We report the case of a patient with ulcerative colitis and autoimmune hemolytic anemia, that improved with steroid therapy, and during the follow-up showed analytical changes of iron deficiency anemia and anemia of chronic disorders. We discuss the possible etiologies of the anemia in patients with ulcerative colitis, and the treatments suggested for the associated Coombs-positive hemolytic anemia in these cases, stressing the good response to steroids in our patient.
Abstract: BACKGROUND: A comparative study of the differences with respect to prevalence, epidemiologic risk factors, clinical and analytical status and histologic data of blood donors with different liver diseases detected in the same geographical area and time period was carried out. METHODS: HBsAg or anti-HCV positive blood donors detected in Asturias (Spain) from October 1989-1991, and a third group of 115 consecutive donors with negative viral markers and an increase in ALT, as well as a fourth control group with no alterations were compared with a BMDP statistical program and logistic regression analysis. RESULTS: The prevalence of anti-HCV+ donors was greater than that of those with HBsAg+ in both general donors (0.87% vs 0.28%) as well as in new donors (1.77% vs 1.2%) with a constant incidence of HBsAg+ cases of around 0.16% of the donations with a decrease being observed in the anti-HCV+ (ELISA 1) cases from 0.76% to 0.25%. The mean age was significantly higher among the anti-HCV+ donors with respect to the remaining groups (41 vs 36 years). Likewise, the cases of anti-HCV+ presenting parenteral risk factors, such as intravenous drug addiction, transfusion or surgery were significantly higher, with the latter two having an independent predictive value. Signs or symptoms of liver disease were more frequently detected in the anti-HCV+ (10.8%) vs the HBsAg+ (2.3%) as were an increase in ALT (52.8% vs 12.7%) and histologic signs of chronic hepatitis (36.4% vs 6.9%). CONCLUSIONS: Anti-HCV+ blood donors more frequently present previous parenteral risk factors, signs or symptoms of chronic liver disease, hypertransaminasemia or histologic data of chronic hepatitis, thus its detection in al altruistic blood donor indicates a high probability of chronic subjacent liver disease. This is in contrast to donors with HBsAg+ which do not normally present liver disease and those with hypertransaminasemia with negative viral markers who generally have slight liver lesions.
Abstract: OBJECTIVES: To define the role that sexual transmission plays in the spread of hepatitis C virus (HCV) infection, and to examine the influence of coexistent human immunodeficiency virus (HIV) infection on this mode of transmission. DESIGN: A multicentre, seroprevalence study of anti-HCV performed in the stable heterosexual partners (SHP) of index cases reactive for anti-HCV. SETTING: Department of Internal Medicine and Section of Gastroenterology of three University Hospitals, Spain. SUBJECTS: A total of 423 stable heterosexual partners of index cases reactive for anti-HCV. This included a group of 142 intravenous drug users (IVDU), 120 of whom were coinfected with HIV. Additionally, 2886 first-time voluntary blood donors selected at random were included to compare the prevalence of anti-HCV. MAIN OUTCOME MEASURES: Serum samples were screened for anti-HCV by a commercially available, second-generation enzyme-linked immunoassay. Tests repeatedly reactive for anti-HCV were analysed by a four-antigen, recombinant immunoblot assay. Anti-HIV was tested by enzyme immunoassay and Western blot was used for confirmation of positive cases. RESULTS: The prevalence of anti-HCV, was 7.1% in SHP and 1.2% in random donors (P < 0.001). This prevalence was higher in SHP of index cases coinfected with HIV in comparison with that shown in the SHP of index cases only reactive for the anti-HCV (9.1 vs. 6.3%; P = 0.2), particularly when a younger and more homogeneous group such as the SHP of IVDU index cases was considered alone (9.2 vs. 0%; P = 0.1). However, the SHP of IVDU index cases coinfected with HIV were almost three times more likely to be infected with HIV than HCV (24.2 vs. 9.2%). CONCLUSIONS: These data suggest that HCV infection may be sexually transmitted but with low efficiency, and this could be increased in the presence of coexistent HIV infection in the index case.
Abstract: We report three cases of "Dieulafoy's gastric erosion" or "Exulceratio simplex", which is rarely recognized but is not an uncommon cause of upper gastrointestinal hemorrhage, usually very dangerous, as it's an arterial bleeding. In all cases an emergency endoscopy was performed, and treatment with combination of local sclerosis and vessel's electrocoagulation was successful. We insist in the potential benefits of endoscopic treatment in all these occasions, if it's possible, since even exact diagnosis of the bleeding site is very difficult in some patients.
Abstract: BACKGROUND: The aim of the present study was to know the current prevalence of HBsAg positivity in Asturias blood donors and to carry out a clinical study of the carriers of the hepatitis B virus (HBV) accidentally detected in a blood donation program. METHODS: A prospective study of incidence and prevalence of HBsAg positivity in blood donations performed in Asturias over two years from October 1989 and 1991 was carried out and the epidemiologic, clinical, and analytical characteristics, as well as histologic liver lesions in the HBsAg positive cases were determined. RESULTS: Among the 42,789 blood donors during this above mentioned period in Asturias 119 cases of HBsAg positivity were found, representing a prevalence of 0.16% of the donations and 0.28% of the donors, generally new donors (95.8%) with a prevalence of 1.2% in this subgroup. No risk factors or known source of contagion were found in 43.6% of the cases and in most occasions the donors were asymptomatic HBsAg carriers (96.5%) with normal transaminases (87.3%) with 4.6% of the cases being HBeAg positive and 3.5% being mutant "e minus" carriers. CONCLUSIONS: The prevalence of HBsAg was almost limited to new donors with a higher prevalence being observed with respect to other regions. Most of the cases may be considered as "apparently healthy" and in the group with positive replicative markers a similar number of positive HBeAg carriers and "e minus mutants" were present.
Abstract: BACKGROUND: The aim of this study was to know the prevalence, epidemiology, clinical manifestations and analytical changes present in anti-HCV positive blood donors detected in Asturias. METHODS: A prospective analysis of the incidence and prevalence of anti-HCV positivity in the blood donations carried out in Asturias from October 1989 to October 1991 was performed, as was a clinical and analytical study of the anti-HCV positive cases who attended a clinic specifically created for the same. RESULTS: The prevalence of the anti-HCV was 0.87% of the donors (372/42,789) and 0.50% of the donations (372/73,831) being higher among new donors (1.77%, 165/9,322). Of the 288 cases studied (77.4%), only 51 (17.7%) had been transfused and 105 (36.5%) lacked the previous parenteral risk factor. Only 31 (10.8%) presented symptoms or signs of liver disease and the positivity of the anti-HBc was not associated to any relevant analytical change. The existence of previous major surgery or transfusion was variable with the independent predictive value versus a negative anti-HCV control group. The mean follow up was 12.4 +/- 7.3 months (6-30 months) with an increase in aminotransferases (ALT) being detected in 108 cases (52.7%). A good correlation was found between this data, an ELISA-2 score greater than 5 and RIBA-2 positivity: of the 177 cases in whom RIBA-2 was determined this was found to be positive in 109 (61.6%); 84 cases (77.1%) had an increase in ALT and 100 (91.8%) an ELISA-2 score greater than 5. CONCLUSIONS: In Asturias the prevalence of anti-HCV positivity among blood donors is almost 1% and is greater if new donors are considered, being confirmed by RIBA-2 in 61% of the cases. The subjects are usually asymptomatic and up to one third of the same lack any known risk factor, while almost half have hypertransaminasemia during follow up.
Abstract: We report the case of a 22-year-old man with a craniopharyngioma, who developed ascites following a ventriculoperitoneal shunt procedure for hydrocephalus. The ascites was resolved with diversion of the distal catheter into the right atrium. A ventriculoperitoneal shunt can cause ascites, even without neurological symptoms suggestive of shunt malfunction.
Abstract: In an analysis of the clinical and laboratory variables that can influence the response to interferon alfa-2b treatment, 48 patients with chronic hepatitis C virus infection received interferon 5 million units (MU) subcutaneously three times weekly for eight weeks followed by 3 MU three times weekly for seven months. Response related factors on univariate analysis were found to be age > 40 years, non-parenteral source of infection, pretreatment positive antinuclear antibodies (ANA), cirrhosis, and high serum iron, ferritin, gamma glutamyl transferase, and IgM. An independent predictive value (multivariate analysis) was also found for cirrhosis, ANA, serum iron, and ferritin. A baseline aspartate aminotransferase/alanine aminotransferase ratio of 0.5 and a striking increase during interferon treatment were associated with a complete response.
Abstract: This randomised, controlled trial was designed to assess the response to a nine month course of interferon (IFN) alfa-2b, starting with a higher than usual dose. Forty eight patients received IFN 5 million units (MU) three times a week for eight weeks followed by 3 MU three times weekly for seven months; 25 patients in the control group received no treatment. The overall response to treatment was 68.7%, an improvement over other studies, but the high rate of relapse (85% in patients who responded) suggested that a nine month treatment period was insufficient in most cases. Histological improvement was seen in more than 80% of responders to interferon, including a reduction in inflammatory activity, necrosis, and fibrosis.
Abstract: Sera from 104 patients with self-limited, acute type B hepatitis were tested for the presence of anti-HCV antibodies. The results show that especially drug users with acute type B (and occasionally coinfected with type D) hepatitis commonly are infected with HCV. Furthermore, HCV infection may have preceded infection with the other agents and may be responsible for high ALT levels.
Abstract: We have determined the prevalence of antibodies against hepatitis C virus (anti-HCV) in 45 patients with primary biliary cirrhosis (PBC) and 6 with autoimmune chronic active hepatitis (AI-CAH). Anti-HCV was positive in two cases of PBC, both with a history of previous blood transfusion, and in one patient with AI-CAH, only during an active phase of the disease.
Abstract: The prevalence of antibodies to hepatitis C virus (HCV) was determined in 65 patients with acute non-A, non-B hepatitis (NANBH). The results suggest that HCV is the most common causative agent in posttransfusion NANBH and in drug-related hepatitis. Detection of HCV antibodies does not appear to be a particularly useful diagnostic criterion due to the kinetics of the immune response in the course of the disease.
Abstract: The presence of the anti-HCV antibody was investigated in sera from 102 chronic HBsAg carriers. The subjects varied as to the characteristics of the clinical states. It was found that HCV coinfection was more common in HBsAg positive intravenous drug addicts than in other parenteral risk groups. It also appears that HCV may be the causative agent of chronic liver disease in HBsAg carriers with undetectable HBV (and possibly HDV) replication.
Abstract: To investigate the risk of non-parenteral HCV infection, sera from 302 relatives of 120 anti-HCV positive subjects were tested for the presence of anti-HCV antibodies. For the sake of comparison, sera from 17,000 blood donors were also assayed. The prevalence of HCV positivity was 4.3% in household contacts, compared to 0.78% in the donor population, indicating a significantly higher risk of infection for family members. Close personal contact may not be as critical a factor for infection as is duration of the disease.
Abstract: We studied the prevalence of antibodies to hepatitis C virus (anti-HCV) among 164 heterosexual partners of anti-HCV-positive subjects, 131 prostitutes and 52 homosexual men. 6.7% of heterosexual monogamous partners had anti-HCV; the seropositivity rate was associated with a long-term sexual practice and with age. Of the 131 prostitutes, 6 (4.6%) had anti-HCV; there were significant associations in patients positive for anti-HCV, with a history of parenteral drug addiction. 11.5% of homosexual men were anti-HCV positive; there were significant associations with positivity for antibodies to HIV, intravenous drug abuse and with the number of sexual partners. We concluded that the HCV may be transmitted by sexual route, but the high seroprevalence among prostitutes and homosexuals may be explained by other parenteral mechanisms.
Abstract: We have studied the prevalence of antibody against hepatitis C virus (anti-HCV) and its relation to the time of onset of the symptoms in 57 patients with acute non-A, non-B hepatitis: 16 post-transfusion, 25 drug addicts and 16 sporadic cases. In the 1st month after the onset of illness, anti-HCV was positive in 25% of patients with post-transfusion hepatitis, 44% of drug addicts and 25% of sporadic hepatitis. In the 3rd month this antibody was detected in 75%, 88% and 31.2%, and in the 6th month in 87.5%, 96% and 31.2%, respectively. The prevalence in the 3rd and 6th months was significantly higher in post-transfusion patients and drug addicts than in sporadic cases. In the 6th month the prevalence of anti-HCV in patients who progressed towards chronicity was also significantly higher than in those with acute resolving non-A, non-B hepatitis (94% vs 50%, p less than 0.001). These results show that HCV is probably the main agent in acute post-transfusion non-A, non-B hepatitis and in those occurring in drug addicts, and that in a high proportion of these patients the anti-HCV can be detected in the 3rd month after the beginning of the symptoms. On the other hand, the relation of hepatitis C virus with sporadic acute non-A, non-B hepatitis may be doubtful.
Abstract: We studied the prevalence of antibodies against hepatitis C virus (anti-HCV) among 530 household contacts of 225 anti-HCV-positive subjects (index cases). Twenty-six (4.9%) relatives had anti-HCV, a proportion higher than that found among blood donors (175 of 22,435; 0.78%) (p less than 0.001). We did not find any differences regarding the type of relation with the index case (sexual or nonsexual). The prevalence of anti-HCV increased with the age of the relatives, with the contact time with the index case, and with the time of exposure to HCV. On the other hand, the anti-HCV was associated mainly with the existence of cirrhosis or hepatocellular carcinoma in the patient. We concluded that intrafamilial transmission may be an important mechanism in the spread of HCV.
Abstract: Laparoscopic examinations done during 1979-1989 have been reviewed. From 214 examinations done during the first year of the review, the number of laparoscopies has been steadily declining to 7 examinations in 1989. Indications have also changed during this decade. Laparoscopy does not any more belong to the first choice examinations for diagnosis. Its usefulness is restricted to highly selected individual cases.
Abstract: Pancreatic endocrine tumors are uncommon; of this type of tumors, the Verner-Morrison's syndrome, WDHA or vipoma is diagnosed very rarely. The present paper is a report of a pancreatic vipoma in a 60 year-old female; she presented with watery diarrhea, facial flushing, hypokalemia, hypochlorhydria, metabolic acidosis and reversible renal failure; these are the usual manifestations of the syndrome. The diagnosis was made on the basis of radiological imaging, CAT and arteriography as well as the finding or elevated levels of vasoactive intestinal peptide (VIP). The surgical resection of the tumor was followed by the remission of the symptoms and normalization of the plasmatic levels of VIP. It is necessary to recognize this type of tumors because the only way to achieve a curative surgical resection is after an early diagnosis.
Abstract: The topic of esophagitis due to Candida (ED), the most frequent infection of the esophagus, is reviewed. In recent years we have seen increased interest in candida esophagitis, fundamentally due to its relation with AIDS, for which it constitutes a diagnostic criteria. Candida esophagitis, although it can appear in apparently healthy subjects, is usually associated with processes that impair the immune system, as well as with local lesions of the esophagus. The typical clinical presentation is as odynophagia, dysphagia and/or retrosternal pain, although asymptomatic forms are frequent, and its association with oropharyngeal candidiasis is variable. Oral endoscopy is the diagnostic technique of choice, since it permits samples to be taken for histologic and cytologic study and cultures; cytology is the most sensitive and specific technique. The differential diagnosis should be made fundamentally with other infectious esophagitis pictures, particularly herpes, and with reflux esophagitis. Treatment is based on antifungal drugs, most frequently nystatin, amphotericin B and ketoconazole.
