Prevalence and factors associated with faecal impaction in the Spanish old population.

Background: Faecal impaction (FI) is a common problem in old people living in nursing home. Its prevalence and associated factors remain unknown in the general population. Aim: To evaluate FI prevalence in the Spanish population older than 65 years and to assess the factors associated with it. Methods: A telephone survey was carried out of a Spanish population older than 65 years random sample (N = 1000). FI was assessed using a previously validated questionnaire. Results: A total of 28,128 calls were made; 1,431 subjects were eligible and 1,000 subjects were enrollled, mean aged 74.6 ± 7.3 (65­97); 57.5% were women. At least 53 people reported FI within the past year (5.3% (CI 95%: 3.9­6.7%)). Only 0.03% met criteria for chronic constipation and faecal incontinence. FI-associated factors were constipation, female gender, reduced physical activity, and chronic renal failure (CRF). Conclusion: FI is a prevalent problem in old Spanish population. Constipation and female gender are the main associated factors; low physical activity and CRF appear to play also a significant role. Further studies are required to confirm this association.

Weight Gain and Somatization are Associated With the Onset of Gastroesophageal Reflux Diseases: Results of Two 5-year Follow-up Studies.

BACKGROUND: Although 2% to 4% of the population develop gastroesophageal reflux disease (GERD) annually, factors associated with the onset of GERD are scarcely known. OBJECTIVE: To assess whether such factors include weight gain and psychological distress. METHODS: Two cohorts (first: N=222; second N=754) drawn from 2 case-control studies were followed up for around 5 years. In 2004, all participants were directly interviewed using a validated questionnaire to collect data on body weight, height, GERD symptoms, and psychological distress. In 2009 to 2010, these same participants were again interviewed using the same methodology. RESULTS: The response rate was 83.3% in cohort 1 and 39.1% in cohort 2, after a follow-up of 4.3±0.7 and 5.6±0.3 years, respectively. The multivariate analysis showed only weight gain and psychological distress as being independently associated with the onset of GERD in both cohorts. Weight gain per kilogram showed an adjusted odds ratio (OR) of 1.21 (1.01-1.44) in the first cohort, and a gain of 5 kg or more showed an adjusted OR of 4.65 (1.72-12.53) in the second. Somatization scores showed an adjusted OR of 1.09 (1.04-1.15) in the first cohort (measured as Minnesota Multiphasic Personality Inventory 2 hypochondriasis score) and 2.88 (1.04-8.02) in the second (measured as psychosomatic symptoms score). Body mass index on attaining overweight or obese status was associated with the onset of GERD in the unadjusted but not in the adjusted analysis. CONCLUSIONS: Weight gain and somatization are the main factors associated with the onset of GERD. The association between GERD and obesity is just the ultimate consequence of gaining weight.

Is the reflux disease questionnaire useful for identifying GERD according to the Montreal definition?

BACKGROUND: Scales for aiding physicians diagnose gastro-oesophageal reflux disease (GERD) have not been evaluated in terms of their ability to discriminate between troublesome symptoms (TS) and non-troublesome symptoms (NTS). Our objective is to evaluate the ability of the Reflux Disease Questionnaire (RDQ) to identify GERD according to referral of TS, in patients without previous proton pump inhibitor (PPI) treatment and in patients on PPI treatment. METHODS: Patients consulting physicians because of heartburn or acid regurgitation were recruited at 926 primary-care centres in Spain. They were asked to complete several questionnaires including the RDQ, and to define which of their symptoms were troublesome. Information on drug treatment was collected by the physician. We performed a receiver operating characteristic (ROC) curve analysis to ascertain the RDQ's optimum cut-point for identifying TS. RESULTS: 4574 patients were included, 1887 without PPI and 2596 on PPI treatment. Among those without PPI treatment, 1722 reported TS. The area under the curve (AUC) was 0.79 for the RDQ, and the optimum RDQ cut-point for identifying TS was 3.18 (sensitivity, 63.2%; specificity, 80.2%). A total of 2367 patients on PPI treatment reported TS, and the optimum RDQ cut-off value was 3.06 (sensitivity, 65.4%; specificity, 71.8%). CONCLUSIONS: An RDQ score higher than 3 shows good sensitivity and specificity for differentiating TS from NTS among patients without PPI or on PPI treatment. The RDQ is useful in primary care for diagnosis of GERD based on the Montreal definition.

Validation of a questionnaire for assessing fecal impaction in the elderly: impact of cognitive impairment, and using a proxy.

BACKGROUND: Studies on the epidemiology of fecal impaction are limited by the absence of a valid and reliable instrument to identify the condition in the elderly. Our aim is to validate a questionnaire for identifying fecal impaction in the elderly and to assess the impact of cognitive impairment and the aid of a proxy on its reliability. METHODS: We developed a 5 questions' questionnaire. The questionnaire was presented to twenty doctors to test its face validity. Feasibility was pre-tested with ten non institutionalized subjects who completed the questionnaire twice, once alone or with the help of a proxy, and another along with the researcher.For the validation of the questionnaire all residents in a single nursing-home were invited to participate, allowing the self-decision of using a proxy. Medical records of all subjects were abstracted without knowledge of subjects' answers and agreement between fecal impaction according to self-reported and medical records analyzed. Physical impairment was measured with the Barthel's test and cognitive impairment with the mini-mental test. RESULTS: In the face validity only minor changes in wording were suggested. In the feasibility pre-test all subjects were able to understand and complete the questionnaire and all questions were considered appropriate and easily understandable.One-hundred and ninety-nine of the 244 residents participated in the study (mean age 86,1 ± 6,6). One hundred and forty two subjects understood all questions; not understanding them was inversely associated with cognitive impairment score (aOR: 0.86; 95% CI: 0.82-0.91). One hundred and sixty decided to use a proxy; the use of a proxy was inversely associated with educative level (0.13 (0.02-0.72), minimental's score (0.85; 0.76-0.95) and Barthel's score (0.96; 0.94-0.99). Agreement between medical records and self-completed questionnaire was 85.9% (kappa 0.72 (0,62- 0,82). Disagreement was unrelated to education and cognitive impairment. CONCLUSIONS: Our simple questionnaire is reliable for identifying fecal impaction in the elderly by self-report. Limitation imposed by cognitive impairment is minimized with the aid of a proxy.

Advantages of early cholecystectomy in clinical practice of a terciary care center.

BACKGROUND: Despite a number of studies show the superiority of early over delayed cholecystectomy in the treatment of acute cholecystitis, there is still controversy over the time for intervention. This study aimed to assess the use of early versus delayed cholecystectomy for the treatment of acute cholecystitis in terms of complications, conversion to open surgery and mean hospital stay. METHOD: We collected patients with acute cholecystitis treated at a referral center for a year, and retrospectively analyzed the chosen therapeutic approach, the percentage of conversion of early cholecystectomy to open surgery, appearance of surgical complications, and mean hospital stay. RESULTS: The study included 117 patients, 44 women and 73 men, who had a mean age of 67.36+/-15.74 years. Early cholecystectomy was chosen in 31 (26.5%) and delayed cholecystectomy in 74 patients (63.2%). Of the 74 patients, 28 (37.8%) required emergency performance of delayed cholecystectomy, and 19 (25.7%) had not undergone surgery by the end of the study. While no differences were observed between early and delayed cholecystectomy in terms of surgical complications and conversion to open surgery, mean hospital stay was nevertheless significantly shorter in the early versus the delayed cholecystectomy group (8.32+/-4.98 vs 15.96+/-8.89 days). CONCLUSION: Under the routine working conditions of a hospital that is neither specially dedicated to the surgical treatment of acute cholecystitis nor provided with specific management guidelines, early cholecystectomy can reduce the hospital stay without increase of the conversion rate or complications.

Polymorphism of the TLR4 gene reduces the risk of hepatitis C virus-induced hepatocellular carcinoma.

OBJECTIVE: Toll-like receptor 4 (TLR4) signalling participates in the innate immune response against hepatitis C virus (HCV) infection. TLR4 gene polymorphisms may influence the risk of HCV-induced hepatocellular carcinoma (HCC). This is a single-centre-based study designed to analyse the distribution of several TLR4 gene single nucleotide polymorphisms in healthy controls and in patients chronically infected with HCV, with and without HCC. METHODS: We have determined three single nucleotide polymorphisms (rs2149356, rs4986791 and rs5030719) at the TLR4 gene in 155 patients with HCV-related HCC, 153 patients with chronic hepatitis C and 390 healthy controls. All were white and most were Spaniards. RESULTS: (1) rs5030719 was monomorphic and was not further analysed; (2) the rs2149356 T allele carrier state was significantly less frequent in patients with HCC than in healthy controls (OR 0.421, 95% CI 0.285-0.625) and in patients with chronic hepatitis C (OR 0.426, 95% CI 0.236-0.767); (3) the proportion of rs2149356 T allele carriers progressively diminished with increasing clinical stage of HCC; (4) no significant differences were observed for the rs4986791 T allele. CONCLUSION: The TLR4 rs2148356 T allele is associated with a reduced risk of HCC and could slow down its clinical progression in HCV-induced chronic liver disease.

Predicting response to therapy in chronic hepatitis C: an approach combining interleukin-28B gene polymorphisms and clinical data.

BACKGROUND AND AIM: Polymorphisms at the interleukin-28B (IL28B) gene predict therapeutic response in chronic hepatitis C virus genotype 1 (CHC-1) infection. The aim of the present study was to establish whether a unique single-nucleotide polymorphism (SNP) represents the whole predictive value of the IL28B haplotype for sustained viral response (SVR) and primary non-response (PNR). METHODS: SNP rs12979860 and rs8099917 were determined by TaqMan assays in 110 CHC-1 Caucasian patients treated with pegylated interferon plus ribavirin. RESULTS: There were 51 SVR, 43 PNR, and 16 relapses. Baseline predictors of SVR were rs12979860CC genotype (P = 0.008), viral load < 400.000 IU/mL (P < 0.010), age (P = 0.013), γ-glutamyl transferase (P = 0.022), alkaline phosphatase (P = 0.008), and cholesterol (P = 0.048). The area under the receiver-operating curve (AUROC) of the model, including these variables, was 0.841 (95% confidence interval [CI] = 0.767-0.916). The same figures for PNR were rs12979860 T-allele carrier state (P = 0.00008), viral load ≥ 400.000 IU/mL (P = 0.007), aspartate aminotransferase/alanine aminotransferase (P = 0.048), and serum cholesterol (P = 0.064), (AUROC = 0.869, 95% CI = 0.792-0.945). After excluding rs12979860CT SNP from multivariate analyses, the rs8099917 genotype alone did not predict SVR (P = 0.185), but strongly predicted PNR (P = 0.003). The significance of haplotypes combining both SNP as predictors of SVR and PNR was higher than those of each separate SNP. CONCLUSIONS: The rs12979860 SNP strongly predicts therapeutic response in CHC-1 patients, and if associated with easy-to-obtain baseline criteria, provides a useful tool for the selection of candidates for antiviral therapy. IL28B haplotypes might improve the clinical usefulness of individual SNP.

The burden and management of patients with IBS: Results from a survey in spanish gastroenterologists.

BACKGROUNDS: irritable bowel syndrome (IBS) is a common and complex disorder. Though it is estimated that IBS constitutes an important part of the gastroenterology (GI) practice, the burden of this problem in the GI outpatients clinics in Spain is unclear. AIM: the aim of this study is to obtain a "shot" of the burden and management of this syndrome in the daily GI practice. METHODS: 508 general gastroenterologists from all over the country were approached and asked to complete a survey that included questions about their daily practice and the definition, diagnosis and treatment of IBS. RESULTS: 55% of the surveyed physicians estimate that IBS constitute between a quarter and a half of all their consultations; and pointed out that most of these patients were referred from primary care. Overall, the Spanish gastroenterologists show an adequate knowledge of the different diagnostic criteria, though they do not always follow the current guidelines. Up to 55% of the physicians always perform a complementary test to support their diagnosis and 40% order a diagnostic test only in older patients (> 50 years) or in presence of alarm symptoms. Interestingly, 80% of the gastroenterologists start empirical treatment based on the patients' symptoms. CONCLUSIONS: though Spanish gastroenterologists seem to have an adequate theoretical knowledge of the disease, they do not systematically follow current guidelines and tend to manage IBS symptoms based on their own criteria.

Translation, cultural adaptation and validation of a Spanish version of the Irritable Bowel Syndrome Severity Score.

BACKGROUND: the Irritable Bowel Syndrome Severity Score (IBSSS) is a questionnaire only available in English that classifies IBS patients according to the severity of their symptoms and can be used to guide and monitor the treatment. AIMS: to adapt and validate into Spanish the English version of the IBSSS questionnaire. METHODS: the Spanish version of the questionnaire was obtained through a process of translation-evaluation of the comprehensibility and back translation. In a later phase we evaluated the applicability(n = 15), reproducibility (n = 31) and sensitivity to change (n = 40) of the Spanish version of the questionnaire. Finally we evaluated an alternative version of the ISBSS using a numerical scoring system instead of the original analog visual scale (n = 40). RESULTS: the Spanish version of the IBSSS showed an excellent reproducibility (r = 0.81 for global score) and an adequate sensitivity to change: a decrease of 45 points or more identified worsening of IBS with a 70.6% sensitivity and 87.5% specificity; an increase of 45 points or more identified improvement of IBS with a 85.7% sensitivity and 87.5% specificity. The severity score was practically the same regardless of the scoring system used (r = 0.96). CONCLUSIONS: the Spanish version of the IBSSS is a reproducible tool that is able to identify relevant changes over the course of the disease. The use of a numerical scoring system is a valid alternative to the visual scale that improves the applicability of the questionnaire to situations when the written communication is limited or not possible.

Non-invasive evaluation of the fibrosis stage in chronic hepatitis C: a comparative analysis of nine scoring methods.

OBJECTIVE: Liver biopsy is an invasive procedure and new surrogate markers to assess fibrosis are needed. We performed a comparative external evaluation of nine non-invasive scores of liver fibrosis and tried to identify other potential biochemical markers of low-stage liver fibrosis in chronic hepatitis C (CHC). MATERIAL AND METHODS: We included 429 previously untreated consecutive patients from a single centre who underwent a liver biopsy between January 1999 and April 2009. Biopsies were evaluated for the stage of fibrosis according to the METAVIR scoring method. RESULTS: None of the evaluated scores were adequate to disclose null-low fibrosis due to a lack of specificity at the proposed cut-offs and the poor sensitivity of lower cut-offs. Serum ferritin and cholesterol values were found to be independently related to the fibrosis stage and their inclusion in the best performing scores at lower cut-off values (the APRI and King's scores) improved the sensitivity for null-low fibrosis by 8% with a specificity >or= 93%. CONCLUSIONS: Approximately 30% of patients with null-low fibrosis may be accurately identified by supplementing current scores with new independent variables (serum ferritin and cholesterol), thus obviating the need for a liver biopsy.

Prevalence of functional gastrointestinal disorders in patients with fibromyalgia and the role of psychologic distress.

BACKGROUND & AIMS: Fibromyalgia is a rheumatologic disorder associated with somatic and psychologic conditions. Although fibromyalgia is associated with irritable bowel syndrome, its relationship with other functional gastrointestinal disorders (FGID) is unclear. We evaluated the prevalence of FGID in patients with fibromyalgia and the role of psychologic factors in this relationship. METHODS: From a Spanish population, 100 patients with fibromyalgia and 100 matched controls completed the Rome II Integrative Questionnaire to assess the prevalence of FGID and the Symptom Checklist-90 Revised (SCL-90R) to evaluate psychologic distress. Patients completed the Fibromyalgia Impact Questionnaire to evaluate the overall impact of fibromyalgia and controls filled out the Chronic Widespread Pain Questionnaire to detect potential cases of fibromyalgia. RESULTS: Ninety-three percent of the total study population was female, with a mean age of 50 years. We identified 6 cases of widespread pain among controls. The average Fibromyalgia Impact Questionnaire score for patients was 67.28 +/- 14.25. All gastrointestinal symptoms except for vomiting were more frequent in patients. Ninety-eight percent of patients with fibromyalgia had at least one FGID, compared with only 39% of controls. Fibromyalgia was correlated most highly with irritable bowel syndrome. Patients presented with significantly higher scores of psychologic distress than controls, especially those with fecal incontinence. CONCLUSIONS: There is a prevalence of FGID in patients with fibromyalgia and a wider distribution of such symptoms along the gastrointestinal tract compared with controls. We propose that an increased degree of psychologic distress in these patients predisposes them to FGID, especially significant for anorectal syndromes.

Novel association of the interleukin 2-interleukin 21 region with inflammatory bowel disease.

OBJECTIVES: Genome-wide association studies have reported the role of the interleukin (IL) 2-IL21 chromosomal region at 4q27 in several autoimmune conditions. Mice deficient in IL-2 develop a disease with clinical and histological similarity to ulcerative colitis (UC) in humans. Modest evidence of linkage with UC was tentatively proposed for the IL2 gene more than a decade ago. Therefore, we decide to investigate the association of polymorphisms in the IL-2 axis (IL2, IL2RA, and IL2RB genes) with inflammatory bowel diseases (IBDs). METHODS: Seven hundred and twenty-eight white Spanish unrelated IBD patients (356 Crohn's disease (CD) and 372 UC) and 549 ethnically matched controls were included in a case-control study. In addition, a Spanish replication cohort with 562 CD and 430 UC patients and 1,310 controls were analyzed. Eight single-nucleotide polymorphisms previously associated with different autoimmune diseases were analyzed using TaqMan chemistry. RESULTS: The IL2-rs6822844 polymorphism modified CD predisposition (P=0.002; odds ratio, OR (95% confidence interval, CI)=0.61 (0.44-0.84)); this was replicated in the other Spanish cohort, resulting in a strong protective effect of the minor allele in the merged samples (P=0.0002; OR (95% CI)=0.70 (0.58-0.85)). A similar effect of rs6822844 was detected for UC. Another marker, rs11938795, also showed evidence of an association with CD (P=0.006; OR (95% CI)=0.73 (0.58-0.92)). CONCLUSIONS: Polymorphisms within the IL2-IL21 linkage disequilibrium (LD) block show a novel association with IBD, this is concordant with suggestive previous results of whole genome analyses in CD and type 1 diabetes. Our data agree with the effect previously observed for other conditions and delineate a shared underlying mechanism.

Analysis of a non-synonymous single nucleotide polymorphism of the human diamine oxidase gene (ref. SNP ID: rs1049793) in patients with Crohn's disease.

OBJECTIVE: To analyse the possible influence of a non-synonymous single nucleotide polymorphism (SNP) of the histamine-degrading enzyme diamine oxidase (DAO) on genetic susceptibility to Crohn's disease (CD). MATERIAL AND METHODS: In this prospective, case-control study, 210 unrelated Caucasian consecutive CD patients were recruited at the Inflammatory Bowel Disease Unit of a single tertiary centre (Hospital Clínico San Carlos) in Madrid, Spain. A total of 261 healthy volunteers from the same geographic area were also recruited and matched with patients. Both cases and controls were analysed for the presence of a non-synonymous SNP (rs1049793) of DAO using amplification-restriction procedures of the genotype obtained in a blood sample. RESULTS: No significant differences were found in the distribution of carriers of the non-synonymous SNP of DAO between CD patients and controls (OR 1.2 (95% CI 0.9-1.6; p=0.3)). Nor were any differences found between carriers and non-carriers of the non-synonymous SNP in demographic characteristics, phenotypes, complications or treatment of CD. CONCLUSIONS: The study of a non-synonymous SNP (rs1049793) of DAO does not seem to be of use in assessing susceptibility to CD, either as a marker of disease activity or as a marker of clinical behaviour in patients with the disease.

Influence of psychological distress on characteristics of symptoms in patients with GERD: the role of IBS comorbidity.

UNLABELLED: A link between gastroesophageal reflux disease (GERD) and psychological distress has been suggested; psychological factors may modulate the characteristics of symptoms. Besides, irritable bowel syndrome (IBS) frequently coexists with GERD so it may be hypothesized that psychological distress in GERD might be an epiphenomenon of IBS comorbidity. AIMS: Evaluate the association of psychological distress with GERD, the influence of psychological factors on symptoms, whether psychological distress is explained by a subset of GER patients, and if coexistence with IBS would be a surrogate marker. METHODS: We performed a prospective case-control study. Cases were patients diagnosed with GERD reporting heartburn at least 2 days per week as the main complaint. Controls were matched healthy subjects without or occasional symptoms. All individuals completed a set of validated questionnaires to evaluate GERD and IBS symptoms and psychological distress (SCL-90R). RESULTS: Ninety-two patients and 92 controls were included. Fifty-seven patients and six controls fulfilled Rome II criteria for IBS. Body mass index (BMI), somatization, and IBS were independently related to GERD. Patients with and without IBS were not different in any measure of psychological distress. Characteristics of symptoms did not correlate to psychological measures. Cluster analysis isolated a cluster of nondistressed from distressed subjects. A higher proportion of GERD patients than controls were classified as distressed (29.7% versus 7.7%). No variable (including IBS) distinguished nondistressed from distressed GERD patients, except for sex. CONCLUSIONS: Nearly one-third of GERD patients attending a gastroenterologist office are psychological distressed; they cannot be identified by features of symptoms or IBS comorbidity so a specific anamnesis under the scope of a biopsychosocial model is warranted.

Polymorphisms in the selenoprotein S gene: lack of association with autoimmune inflammatory diseases.

BACKGROUND: Selenoprotein S (SelS) protects the functional integrity of the endoplasmic reticulum against the deleterious effects of metabolic stress. SEPS1/SelS polymorphisms have been involved in the increased release of pro-inflammatory cytokines interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-6 in macrophages. We aimed at investigating the role of the SEPS1 variants previously associated with higher plasma levels of these cytokines and of the SEPS1 haplotypes in the susceptibility to develop immune-mediated diseases characterized by an inflammatory component. RESULTS: Six polymorphisms distributed through the SEPS1 gene (rs11327127, rs28665122, rs4965814, rs12917258, rs4965373 and rs2101171) were genotyped in more than two thousand patients suffering from type 1 diabetes, rheumatoid arthritis or inflammatory bowel diseases and 550 healthy controls included in the case-control study. CONCLUSION: Lack of association of SEPS1 polymorphisms or haplotypes precludes a major role of this gene increasing predisposition to these inflammatory diseases.

Determinants of quality of life in irritable bowel syndrome.

OBJECTIVES: Health-related quality of life (HRQOL) is a main outcome in irritable bowel syndrome (IBS), but most studies have been conducted on moderate-severe patients. We sought to ascertain the relative contribution of severity, anxiety, and personality to impairment of HRQOL in a sample representative of the entire IBS spectrum. MATERIALS AND METHODS: IBS consulters, IBS nonconsulters, and controls were invited to complete questionnaires designed to measure severity of IBS (Functional Bowel Disease Severity Index), anxiety (State-trait Anxiety Inventory), personality (Minnesota Multiphasic Personality Inventory-2), and HRQOL [Short Form 36 (SF-36)]. The SF-36 scores of the study groups were compared, and a multiple regression model was constructed. RESULTS: Sixty-six IBS consulters, 70 nonconsulters, and 117 controls were studied. All 3 groups differed in terms of SF-36 physical (46.5+/-9.4 vs. 50.5+/-8.0 vs. 54.5+/-6.0) and mental composite scores (38.2+/-12.5 vs. 43.2+/-12.0 vs. 46.7+/-10.6). Although physical scores were linked to hypochondriasis (beta=-0.39; P<0.001), severity of pain (beta=-0.28; P<0.001), and age, mental scores were associated with state anxiety (beta=-0.36; P<0.001) and trait anxiety (beta=-0.40; P<0.001). CONCLUSIONS: HRQOL is impaired in all subgroups of IBS sufferers, with the degree of impairment depending mostly on symptom severity and psychologic factors (hypochondriasis and anxiety).

Role of the PXR gene locus in inflammatory bowel diseases.

BACKGROUND: The pregnane X receptor gene (PXR/NR1I2) has been recently associated with an increased risk for inflammatory bowel disease (IBD), although a subsequent case-control study failed to replicate the original association in an independent population. This nuclear receptor regulates genes involved in the detoxification process in the liver and intestine, like ABCB1/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC), but remained unaffected in Crohn's disease (CD) patients. Considering previous results, we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population. METHODS: Three PXR polymorphisms, including the 1 more strongly correlated with IBD risk in the initial study at -25385C/T (rs3814055) and the 6 haplotypes conformed by them, were analyzed in 365 UC and 331 CD patients and compared with 550 ethnically matched controls. RESULTS: The overall haplotypic distribution showed a significant difference between UC and CD patients (P = 0.05; chi(2) = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; chi(2) = 17.04), mainly due to the presence of a risk haplotype (rs3814055*T//rs6784598*C//rs2276707*C: P = 0.001; odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.20-2.30). Patients with extensive UC carrying the -25385T allele showed increased susceptibility compared with left-sided colitis patients and with healthy subjects. In patients with extensive UC a significantly different distribution of genotypes of the MDR1 G/A change located in intron 3 (rs3789243) was observed between carriers/noncarriers of the -25385T risk allele (P = 0.005). CONCLUSIONS: Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes.

MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease.

BACKGROUND: To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). METHODS: A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine. RESULTS: A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6-12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8-22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82-3.9; P = 0.14). CONCLUSIONS: The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy.

Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients.

BACKGROUND: Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk. METHODS: CYP3A4 and CYP3A5 genotypes were determined in 574 individuals including 178 patients with primary liver cancer, 82 patients with gastric cancer, 151 patients with colorectal cancer, and 163 healthy individuals. RESULTS: The variant allele frequencies for patients with liver cancer, gastric cancer, colorectal cancer and healthy controls, respectively, were: CYP3A4*1B, 4.8 % (95% C.I. 2.6-7.0), 3.7 % (0.8-6.6) 4.3% (2.0-6.6) and 4.3% (2.1-6.5); CYP3A5*3, 91.8 % (93.0-97.4), 95.7% (92.6-98.8), 91.7% (88.6-94.8) and 90.8% (87.7-93.9). The association between CYP3A4*1B and CYP3A5*3 variant alleles did not significantly differ among patients and controls. No differences in genotypes, allele frequencies, or association between variant alleles were observed with regard to gender, age at diagnosis, tumour site or stage. CONCLUSION: Common polymorphisms on CYP3A4 and CYP3A5 genes do not modify the risk of developing digestive cancers in Western Europe.

[Utility of liver biopsy in the etiologic diagnosis of biochemical liver abnormalities of unknown cause]. / Utilidad de la biopsia hepática en el diagnóstico etiológico de las alteraciones de la analítica hepática de causa incierta.

INTRODUCTION: To establish the diagnostic usefulness of liver biopsy (LB) and its influence on the therapeutic approach in patients with persistent abnormal liver tests of unknown cause. METHODS: The 1135 LB performed between January 1999 and January 2007 were retrospectively evaluated. Patients with a strongly suspected diagnosis were excluded. One hundred and twelve patients with chronic elevation of aminotransferases (103 patients), gamma-glutamyltransferase (GGT) (7 patients) and ferritin (2 patients) were included in the analysis. RESULTS: The most common diagnoses were normal liver (35 patients, group 1), minimal changes (15 patients, group 2), bland steatosis (23 patients, group 3), non-alcoholic steatohepatitis (NASH) (17 patients, group 4), and chronic hepatitis (eight patients, group 5). Three patients had tuberculosis of the liver and the remaining 11 had other diagnoses. Ferritinemia was the only parameter significantly lower in group 1 than in groups 2 (p = 0.038), 3 (p = 0.023), and 4 (p < 0.001). Transaminase levels lacked discriminatory value except in chronic hepatitis (p = 0.008). Alkaline phosphatase levels (p = 0.003) were lower in group 4 than in group 1. Triglyceride levels were higher in group 3 (p = 0.009) and group 4 (p = 0.008) than in group 1. Ultrasonography detected steatosis in 28 of the 40 patients with fatty liver (specificity = 0.94; sensitivity = 0.70). CONCLUSIONS: LB modified the therapeutic approach only in the three patients with hepatic tuberculosis. LB confirmed ultrasonographic findings of steatosis and differentiated bland steatosis from NASH, but did not influence the therapeutic approach. Most patients with normal findings on ultrasonography had normal or near-normal biopsies. The indication for LB should be individualized.