High prevalence of muscle weakness and probable sarcopenia in patients with inflammatory bowel disease.

BACKGROUND: This study aimed to determine the prevalence of probable sarcopenia and sarcopenia in patients with inflammatory bowel disease (IBD) by using the European Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria. METHODS: Sarcopenia was assessed by using the sequential four-step algorithm. (1) Find: Sarcopenia risk by simple clinical symptom index (strength, assistance walking, rise from a chair, climb stairs, and falls [SARC-F questionnaire]). (2) Assess: Probable sarcopenia by low muscle strength on handgrip. (3) Confirm: Confirmed sarcopenia by low appendicular skeletal muscle mass on bioimpedance analysis. (4) Severity: Severe sarcopenia by low 4-m gait speed test. RESULTS: A total of 129 adult patients with IBD younger than 65 years and 50 age- and sex-matched healthy control (HC) participants were included to the study. Handgrip strength, gait speed, and SARC-F scores were significantly lower in patients with IBD than in the HCs (P = 0.032, <0.0001, and <0.0001, respectively). Based on the EWGSOP2 definition, 17.8% of patients with IBD had probable sarcopenia, and six patients had confirmed sarcopenia. According to the ethnicity-based population thresholds, 34.9% of patients with IBD had probable sarcopenia, and two patients had confirmed sarcopenia. Corticosteroid use within the past year was identified as an independent risk factor for low muscle strength (P = 0.012; odds ratio, 4.133), along with advanced age and disease activity. CONCLUSION: One-third of the patients younger than 65 years with IBD had probable sarcopenia, defined as low muscle strength, whereas the incidence of confirmed sarcopenia remained relatively low.

Biologic Therapy Carries a Very Low Risk of Reactivation in Hepatitis B Surface Antigen-Negative Phase of Hepatitis B.

BACKGROUND: The risk of hepatitis B reactivation in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients exposed to biologic agents is not clear. We aimed to investigate the reactivation rate in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients after biologic therapy. METHODS: Patients followed at gastroenterology, rheumatology, and dermatology clinics with a diagnosis of immune-mediated inflam matory diseases were screened. Immune-mediated inflammatory diseases patients exposed to biologic agents with a negative hepatitis B surface antigen and positive hepatitis B core immunoglobulin G antibody were included in the study. RESULTS: We screened 8266 immune-mediated inflammatory disease patients, and 2484 patients were identified as exposed to biologic agents. Two hundred twenty-one patients were included in the study. The mean age was 54.08 ± 11.69 years, and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1-6). The mean biologic agent exposure time was 55 (range: 2-179) months. One hundred and fifty-two (68.8%) patients used a concomitant immunomodulatory agent, and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of hepatitis B surface antigen positivity was seen. Antiviral prophylaxis for hepatitis B was applied to 48 (21.7%) patients. Hepatitis B virus-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients without antiviral prophylaxis had hepatitis B virus-DNA reactivation with a negative hepatitis B surface antigen during exposure to the biologic agent. CONCLUSION: We found 2 reactivations and no hepatitis B surface antigen seroconversion in our cohort. Antiviral prophylaxis for patients exposed to biologic agents may need to be discussed in more detail.

Improving the Computer-Aided Estimation of Ulcerative Colitis Severity According to Mayo Endoscopic Score by Using Regression-Based Deep Learning.

BACKGROUND: Assessment of endoscopic activity in ulcerative colitis (UC) is important for treatment decisions and monitoring disease progress. However, substantial inter- and intraobserver variability in grading impairs the assessment. Our aim was to develop a computer-aided diagnosis system using deep learning to reduce subjectivity and improve the reliability of the assessment. METHODS: The cohort comprises 11 276 images from 564 patients who underwent colonoscopy for UC. We propose a regression-based deep learning approach for the endoscopic evaluation of UC according to the Mayo endoscopic score (MES). Five state-of-the-art convolutional neural network (CNN) architectures were used for the performance measurements and comparisons. Ten-fold cross-validation was used to train the models and objectively benchmark them. Model performances were assessed using quadratic weighted kappa and macro F1 scores for full Mayo score classification and kappa statistics and F1 score for remission classification. RESULTS: Five classification-based CNNs used in the study were in excellent agreement with the expert annotations for all Mayo subscores and remission classification according to the kappa statistics. When the proposed regression-based approach was used, (1) the performance of most of the models statistically significantly increased and (2) the same model trained on different cross-validation folds produced more robust results on the test set in terms of deviation between different folds. CONCLUSIONS: Comprehensive experimental evaluations show that commonly used classification-based CNN architectures have successful performance in evaluating endoscopic disease activity of UC. Integration of domain knowledge into these architectures further increases performance and robustness, accelerating their translation into clinical use.

Improvement of Work Productivity and Quality of Life with Anti-Tumor Necrosis Factor Treatment Used in Crohn's Disease in Routine Clinical Practice in Turkey.

BACKGROUND: Patients with Crohn's disease experience major deterioration in work productivity and quality of life. We aimed to provide the long-term effects of anti-tumor necrosis factor agents on work productivity and activity impairment and quality of life in patients with Crohn's disease using the Inflammatory Bowel Disease Questionnaire and the Short-Form Health Survey-36. METHODS: Patients with Crohn's disease and initiated an anti-tumor necrosis factor treatment were included and followed up for 12 months in this observational study. RESULTS: A total of 106 patients were included in this study, and 64.2% of the patients were males. Mean [± standard deviation] age was 36.8 [± 10.9] years. At baseline, mostly perianal fistulas [65.7%] were observed [n = 23]. Intestinal stenosis was detected in 34.9% of the patients [n = 37], and most of the stenosis was located in the ileum [70.6%] followed by the colon [20.6%]. Extraintestinal symp- toms were observed in 24 patients [22.6%]. Most frequent extraintestinal symptom was arthritis with 71.4% [n = 15]. Mean time from first symptom to initiation of anti-tumor necrosis factor treatment was 6.3 [± 5.0] years. Improvements in work productivity and activ- ity impairment scores throughout 12 months were -24.1% [P = .003] for work time missed, -18.0% [P = .006] for impairment at work, -8.5% [P = .160] for overall work impairment, and -17.0% [P < .001] for daily activity impairment. Similarly, significant improvements [P < .001] were detected in all components of the Inflammatory Bowel Disease Questionnaire when compared to baseline. Statistically sig- nificant improvements [P < .05] were detected for all components of Short-Form Health Survey-36 except for mental health [P = .095]. CONCLUSION: Our study indicates the significant improvement in work productivity and activity impairment and quality of life of patients with Crohn's disease who receive long-term anti-tumor necrosis factor treatment.

Recommendations for Reopening Endoscopy Units in Turkey: A Set-up Plan from a Tertiary Center in Istanbul.

In the midst of Coronavirus-19 (COVID-19) pandemic, endoscopic procedures have been separated for only urgent and semi-urgent cases for the last few months to prevent transmission in endoscopy units. This approach will perhaps resolve the burden of elective procedures in the months ahead of us. As we observe a downtrend in new cases of COVID-19 in Turkey, a strategy for reopening endoscopy units is required. We are stepping into a time period where we should not only re-provide the essential services to our patients but also maintain the safety of healthcare workers and preserve the valuable personal protective equipment as well. Herein, we aim to share the available knowledge in performing endoscopy during the pandemic and the set-up plan of a tertiary center in Istanbul for reopening the endoscopy unit in the era of the COVID-19 pandemic.

Femoral Vein Wall Thickness Measurement May Be a Distinctive Diagnostic Tool to Differentiate Behçet's Disease with Intestinal Involvement and Crohn's Disease.

BACKGROUNDS: Behçet's disease (BD) and Crohn's disease (CD) cannot be easily differentiated in young adults presenting with nonspecific gastrointestinal (GI) manifestations due to similar extraintestinal manifestations. We recently showed that increased common femoral vein (CFV) thickness is a distinctive feature of BD, rarely present in other inflammatory or vascular diseases with a specificity higher than 80% for the cutoff value of ≥ 0.5 mm. We suggest that CFV thickness measurement with ultrasonography (US) can be a diagnostic tool for BD. AIMS: To assess the diagnostic performance of CFV thickness measurement in the differential diagnosis of BD and CD. METHODS: Patients with BD (n = 69), CD (n = 38), and healthy controls (HC) (n = 38) were included in the study. Bilateral CFV thickness was measured with Doppler US. RESULTS: Both right and left CFV thicknesses were significantly higher in BD compared to HC and CD (for right: 0.76 mm vs 0.33 mm, for left: 0.78 mm vs 0.35 mm, p < 0.001 for both). CFV thicknesses in CD were similar to HC (p > 0.05 for both). CFV thickness was also similar between BD patients with and without GI involvement (p = 0.367). The diagnostic cutoff values of ≥ 0.5 mm for CFV thickness performed well against to both CD and HCs for discrimination of BD. The sensitivity and specificity rates were > 85% for both HC and CD. Positive and negative predictive values in our tertiary clinical setting were > 90%. CONCLUSION: We found significantly lower CFV thickness in CD compared to BD. Our results suggest that CFV wall thickness measurement is a distinctive diagnostic tool for the differentiation of BD and CD and can be helpful in daily practice for the differentiation of two diseases.

Validation and reliability of the Turkish version of the inflammatory bowel disease questionnaire for ulcerative colitis and Crohn's disease.

BACKGROUND/AIMS: Inflammatory bowel diseases (IBD) impairs patients' quality of life (QoL). Inflammatory bowel disease questionnaire (IBDQ) is created to measure the health-related QoL specific for IBD. We planned to investigate the validation and reliability of the Turkish translation of IBDQ. MATERIALS AND METHODS: Patients filled self-report questionnaires (Turkish Inflammatory bowel disease questionnaire (TrIBDQ) and Short Form-36 (SF-36)) themselves under a physician's supervision, and they were free to ask questions about the questionnaires. The participants then filled the same questionnaire after at least two weeks. Construct validity, discriminant ability, reliability, and susceptibility to change were analyzed separately for the IBD patients. Intra-class correlation coefficient (ICC) was used to assess test-retest reliability. Cronbach's alpha values were used to assess internal consistency. RESULTS: A hundred patients enrolled in the study, 53 with Crohn's disease (CD), 47 with ulcerative colitis (UC). We found a moderate to high positive correlation between the TrIBDQ domains and the SF-36 dimensions. In UC and CD, TrIBDQ was able to differentiate active disease and remission. We found Cronbach's alpha for TrIBDQ domains ranged from 0.76-0.94 in CD and from 0.79-0.92 in UC. The total Cronbach's alpha for TrIBDQ was 0.96 in CD and 0.95 in UC. Sensitivity-to-change analyses of the bowel, systemic, and emotional scores showed statistically significant differences between their baseline and follow-up values. CONCLUSION: TrIBDQ is a valid and reliable tool for assessing the quality of life in Turkish speaking IBD patients. Thus it can be used in clinical research and practice.

Human dental follicle mesenchymal stem cells alleviate T cell response in inflamed tissue of Crohn's patients.

BACKGROUND/AIMS: Crohn's Disease (CD) is a chronic inflammatory condition characterized by various abnormalities that lead to overly aggressive T-cell responses. Our in vitro experiments aimed to investigate the potential use of Dental Follicle Mesenchymal Stem Cells (DF-MSCs) to suppress the exaggerated immune response in inflamed and non-inflamed tissue of Crohn's Disease (CD). MATERIAL AND METHODS: Dental follicle tissues were obtained from extracted third molar teeth of 3 healthy volunteers who have no abscess or inflammatory diseases. Eleven patients included the experiment who had been diagnosed with CD and not received steroid maintenance therapy for more than 1 month. Mononuclear Cells (MNCs) were isolated from inflamed and non-inflamed tissue of CD. Isolated cells were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the presence and absence of DF-MSCs and analyzed for lymphocytes proliferation capacity and viability, T lymphocyte subsets, CD4+IL22BP and CD4+CD25+Foxp3+ regulatory T cell (Tregs) frequencies and cytokine levels. RESULTS: A significant downregulation of lymphocyte proliferation and CD4+IL22BP T cell ratio were found in inflamed cultures with DF-MSCs (p<0,005). Also, the frequency of Tregs increased with DF-MSCs (p<0,05). Pro-inflammatory cytokine levels (TNF-α and IL-6) were decreased (p<0,05) and IL-10 levels were increased (p<0,05) in the supernatant of inflamed cultures. CONCLUSION: DF-MSCs reduced the inflammatory immune response, induced Tregs and downregulated CD4+IL22BP T cell ratio in inflamed samples of CD patients, which may be exploited for significant therapeutic use.

External validation of the Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients.

OBJECTIVES: Toronto hepatocellular carcinoma risk index is developed to stratify cirrhotic patients according to 10-year hepatocellular carcinoma risk. We aimed to validate the performance of Toronto hepatocellular carcinoma risk index in a large Turkish cohort. MATERIALS AND METHODS: We retrospectively reviewed the database of 1287 cirrhotic patients followed-up in a 10-year period (February 2008 to January 2018). All patients were stratified into three groups based on the Toronto hepatocellular carcinoma risk index score as follows: low-risk, < 120; intermediate risk, 120 to 240; and high risk, > 240. Area under the curve and optimal cutoff value of Toronto hepatocellular carcinoma risk index were obtained from receiver operator curve. To reveal the parameters related with hepatocellular carcinoma development, logistic regression analysis was conducted. The cumulative incidences of hepatocellular carcinoma were calculated using the Kaplan-Meier method, and the curves were compared using the log-rank test. RESULTS: Out of 403 enrolled patients, 57 developed hepatocellular carcinoma. The median Toronto hepatocellular carcinoma risk index value was higher in hepatocellular carcinoma (+) group comparing to hepatocellular carcinoma (-) group [267 (70-366) vs. 224 (36-366), P < 0.001]. Out of 57 detected hepatocellular carcinomas, 45 (78.9%) were high risk, 11 (19.3%) were intermediate risk, and only one (1.8%) was low risk at the entry. The area under the curve of the Toronto hepatocellular carcinoma risk index to predict hepatocellular carcinoma was 0.750 (95% confidence interval, 0.683-0.817, P < 0.001). The optimal cutoff value of Toronto hepatocellular carcinoma risk index was 239.5, giving a sensitivity of 78.9% and specificity of 62.7%. As a result, Toronto hepatocellular carcinoma risk index remained to be the only significant parameter that has an affect on hepatocellular carcinoma development [adjusted-odds ratio: 1.016 (95% confidence interval, 1.007-1.024), P<0.001]. CONCLUSION: The present study validated the performance of Toronto hepatocellular carcinoma risk index in Turkish cirrhotic patients to predict hepatocellular carcinoma risk, which can be considered as a tool for personalized surveillance.

Clinical significance of isolated abnormal intestinal findings in magnetic resonance enterography in patients with suspected small bowel disease.

PURPOSE: Magnetic resonance imaging (MRE) is a well-established adjunct diagnostic tool for the diagnosis of Crohn's Disease (CD), as ileocolonoscopy can sometimes be falsely reassuring when CD skips distal terminal ileum. We aimed to determine the frequency and clinical significance of isolated abnormal small bowel findings in MRE with normal ileal view in ileoscopy. METHODS: We retrospectively reviewed findings from 1611 MRE studies that were conducted between 2012 and 2018 to detect patients bearing abnormal intestinal findings and having full ileocolonoscopy. After exclusion of normal or repetitive MRE scans and previously known CD, 147 patients with abnormal MRE detected. MRE scans were categorized as suspicious of CD and non-specific findings. RESULTS: Out of 147 patients with abnormal MRE, 122 (83%) had terminal ileum involvement in MRE consistent with ileoscopy findings. Twenty-five (17%) patients were found to have solitarily abnormal intestinal findings in MRE with normal ileoscopy. Only 3 (12%) were diagnosed with CD initially, and all had MRE findings suspicious of CD. The remainder 40% (n = 10) were diagnosed with non-Crohn's small bowel disease after further investigation, while in the other 48% (n = 12) abnormal MRE findings could not be explained with any organic disease in the follow-up. CONCLUSION: The present study demonstrated that only a small portion of patients with isolated abnormal intestinal findings in MRE is CD, and more than that are non-crohn's small bowel diseases. These findings, even if they carry the suspicion of CD, do not transform to CD in the long-term follow-up.

The Effect of Dream Anxiety on Sleep Quality in Inflammatory Bowel Diseases.

INTRODUCTION: Declining sleep quality is a well-known issue in inflammatory bowel disease (IBD), but dream characteristics of patients with IBD and their role in sleep quality are unknown. In this study, we aimed to examine whether and how patients with ulcerative colitis (UC) and Crohn's disease (CD) differ on sleep quality, sleepiness level, and dream anxiety (DA) level compared to healthy controls (HC), controlling for their depressive and anxious tendencies. METHODS: Patients and HCs were enrolled prospectively into the study. The Van DA Scale, Pittsburg Sleep Quality Index, Epworth Sleepiness Scale, Beck Depression Index, and State-Trait Anxiety Inventories were used to assess DA, sleep quality, sleepiness, depression, and anxiety, respectively. RESULTS: Patients with IBD had significantly lower depression (p = 0.004), state anxiety (p = 0.0001), trait anxiety (p = 0.004), and DA (p = 0.0001) than HCs. Although no statistically significant difference in sleep quality was found (p = 0.99), daytime sleepiness was more common in HCs than in IBD patients (p = 0.0001). No statistically significant difference was seen in depression, state anxiety, trait anxiety, DA, sleep quality, and daytime sleepiness between patients with CD and those with UC. No correlation was found between disease activity indices and psychological parameters. CONCLUSION: In contrast to previous studies, this study found lower anxiety and depression levels in patients with IBD than in HCs. Moreover, DA score was higher in HCs. For the first time, we revealed that DA may be one of the factors leading to sleep disturbance in patients with IBD.

Effect of gender on the etiology of fecal incontinence: Retrospective analysis of a tertiary referral center in Turkey.

BACKGROUND/AIMS: Anorectal diseases, including fecal incontinence, are prevalent and have an enormous impact on the quality of life. Therefore, investigating their etiological factors may help to reduce the incidence and/or the severity of the underlying diseases. MATERIALS AND METHODS: Referral complaints (constipation, strained defecation, and incontinence) and medical and anorectal manometry records of 883 (562 female/321 male, ages 45.17±1.00 and 48.41±0.63 years, respectively) patients were evaluated retrospectively. Maximal resting pressure (MRP) and maximal squeeze pressure (MSP) measured by stationary pull-through technique, volume of rectoanal inhibitory reflex, and sensory threshold to rectal balloon distention (ST) were obtained by water perfusion system. Data were compared according to referral complaints, age, gender, parity, and underlying diseases. RESULTS: Incontinence was the most frequent referral complaint in 61.2% of females and 67.6% of males. MRP and MSP were significantly lower in incontinent females than in the other groups. In incontinent males, MSP was lower than the strained defecation group, and ST was higher than the constipation group. Age was negatively correlated with MRP for both of the genders and in all groups. Obstetric trauma (85%) and number of parity (3.40±2.59) were significantly higher in incontinent females. Moreover, the most prevalent underlying disease was diabetes in incontinent females (13.7%) and neurological diseases, including traumas, in incontinent males (41.5%). CONCLUSION: Increasing awareness of labor safety, controlling diabetes mellitus, and preventing obstetric traumas may reduce the prevalence of fecal incontinence.

Treatment of Hermansky-Pudlak syndrome Associated granulomatous colitis with anti-TNF agents: case series and review of literature.

Hermansky-Pudlak syndrome is a rare syndrome characterized by bleeding diathesis due to platelet dysfunction, oculocutaneous albinism and other systemic involvements. Granulomatous colitis may occur in the disease course and have similarities with Crohn's disease. Herein, we present four cases with Hermansky-Pudlak syndrome associated colitis with the longest follow-up period having various responses to different anti-TNF agents. Four patients with Hermansky-Pudlak syndrome colitis were started on anti-TNF agents between 2008 and 2013. After a mean follow-up period of 7.5 years, two of four patients exhibited a significant improvement in symptoms, whereas the other two experienced undesirable disease course. Although having many similarities with Crohn's disease; Hermansky-Pudlak syndrome colitis appears to have lower anti-TNF response rates. Pathophysiological differences need to be enlightened to find more appropriate therapeutic targets for Hermansky-Pudlak syndrome colitis.

Incidence rate of anemia in inflammatory bowel diseases.

BACKGROUND/AIMS: To determine the incidence rate and distribution of anemia types over time from an Inflammatory Bowel Disease (IBD) patient cohort spanning 18 years. MATERIALS AND METHODS: Between January 1995 and November 2013, the University Hospital digital databases as well as hard copies of patients' files were reviewed retrospectively. IBD patients with at least one complete blood count (CBC) report were included in this study. RESULTS: We obtained 941 IBD patients' records; 375 (39.9%) patients were diagnosed with Crohn's disease (CD), and 566 (60.1%) patients had ulcerative colitis (UC). Anemia was detected in 548 (58.2%) patients. Female patients were more frequently anemic than male patients (68.4% vs. 49.7%, p=0.001). The frequency of anemia was slightly higher in patients with CD (62.1%) than in patients with UC (55.7%) (p=0.04). The incidence rate of anemia for the entire IBD patient cohort was calculated as 103.45 per 1,000 patient-years. The correlation between the age of the IBD disease and the presence of anemia exhibited a high correlation coefficient of Pearson's r=0.702. CONCLUSION: This is the first study to report the incidence rate of anemia (103.45 per 1,000 patient-years) in a long-term cohort of IBD patients.

Bactericidal permeability increasing protein gene polymorphism is associated with inflammatory bowel diseases in the Turkish population.

BACKGROUND/AIMS: Inflammatory bowel disease, a chronic inflammatory disease with unknown etiology, affects the small and large bowel at different levels. It is increasingly considered that innate immune system may have a central position in the pathogenesis of the disease. As a part of the innate immune system, bactericidal permeability increasing protein has an important role in the recognition and neutralization of gram-negative bacteria. The aim of our study was to investigate the involvement of bactericidal permeability increasing protein gene polymorphism (bactericidal permeability increasing protein Lys216Glu) in inflammatory bowel disease in a large group of Turkish patients. PATIENTS AND METHODS: The present study included 528 inflammatory bowel disease patients, 224 with Crohn's disease and 304 with ulcerative colitis, and 339 healthy controls. RESULTS: Bactericidal permeability increasing protein Lys216Glu polymorphism was found to be associated with both Crohn's disease and ulcerative colitis (P = 0.0001). The frequency of the Glu/Glu genotype was significantly lower in patients using steroids and in those with steroid dependence (P = 0.012, OR, 0.80; 95% confidence interval [CI]: 0.68-0.94; P = 0.0286, OR, 0.75; 95% CI: 0.66-0.86, respectively). There was no other association between bactericidal permeability increasing protein gene polymorphism and phenotypes of inflammatory bowel disease. CONCLUSIONS: Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn's disease and ulcerative colitis. This is the first study reporting the association of bactericidal permeability increasing protein gene polymorphism with steroid use and dependence in Crohn's disease.

No association between the functional cannabinoid receptor type 2 Q63R variants and inflammatory bowel disease in Turkish subjects.

BACKGROUND/AIMS: The endocannabinoid system can exert beneficial effects on gastrointestinal inflammation, and cannabinoid receptor-2 (CB2) agonists may represent a new therapeutic approach in inflammatory bowel disease (IBD). A functional CB2 Q63R polymorphism (rs35761398) in the CNR2 gene has been shown to affect the immunomodulating properties of the CB2 receptor. We sought to investigate whether the functional CB2 Q63R polymorphism (rs35761398) is associated with IBD susceptibility in a Turkish clinical sample. MATERIALS AND METHODS: A total of 202 IBD patients, comprising 101 Crohn's disease (CD) patients and 101 ulcerative colitis (UC) patients, and 101 healthy controls were included in the study. The CB2 Q63R polymorphism was genotyped using real-time PCR. RESULTS: There were no significant differences in the genotype frequencies of the three study groups. The odds ratio of the minor Q allele for CD relative to the common R allele was not significant (OR =1.02, 95% CI =0.67-1.56, p=0.99). Similarly, the odds ratio of the minor Q allele for UC relative to the common R allele did not reach statistical significance (OR =1.10, 95% CI =0.72-1.68, p=0.75). Moreover, the genotype frequencies did not show any significant association with the disease extent in either CD (p= 0.71) or UC patients (p=0.59). CONCLUSION: These pilot findings suggest that CB2 Q63R polymorphism does not play a major role in genetic susceptibility to IBD or in its disease phenotypes among Turkish subjects.

Serum osteopontin levels as a predictor of portal inflammation in patients with nonalcoholic fatty liver disease.

BACKGROUND: Osteopontin is a secreted phosphorylated glycoprotein that is expressed by a variety of cell types and that mediates numerous and diverse biological functions. Osteopontin knockout mice are protected from obesity-induced hepatic steatosis. In the present study, we sought to investigate whether serum osteopontin concentrations are associated with liver histology in patients with nonalcoholic fatty liver disease. METHODS: Serum levels of osteopontin were measured by enzyme-linked immunosorbent assay in 179 well-characterized patients with nonalcoholic fatty liver referred for liver histology and 123 control subjects. RESULTS: Serum osteopontin levels were markedly higher in patients with nonalcoholic fatty liver disease than in controls (p<0.001). Multivariable analysis showed that osteopontin levels were strongly and independently associated with both portal inflammation (ß=0.294, p<0.01) and serum aminotransferase levels (aspartate aminotransferase: ß=0.295, p<0.01; alanine aminotransferase; ß=0.285, p<0.01). CONCLUSION: In summary, these data demonstrate that serum levels of osteopontin are elevated in nonalcoholic fatty liver disease and are a significant independent predictor of portal inflammation in this clinical entity.

Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease.

OBJECTIVES: We sought to determine whether serum concentrations of fibroblast growth factor 19 (FGF19) - an ileum-derived enterokine which plays a role in the control of glucose and lipid homeostasis - are altered in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). DESIGN AND METHODS: Serum levels of FGF19 were measured using enzyme-linked immunosorbent assay in 91 patients with biopsy-proven NAFLD and 74 controls. RESULTS: FGF19 levels were significantly lower in patients with biopsy-proven NAFLD (median: 130pg/mL) than in controls (median: 210pg/mL, P<0.001). Serum FGF19 levels were significantly but modestly associated with hepatocyte ballooning scores in univariate analysis (r=-0.25, P<0.05) but not after adjustment for potential confounders (ß=-0.18; t=1.78, P=0.08). CONCLUSIONS: This pilot study suggests that serum FGF19 levels are decreased in patients with NAFLD but are not independently associated with liver histology findings.

Association between bactericidal/permeability increasing protein (BPI) gene polymorphism (Lys216Glu) and inflammatory bowel disease.

BACKGROUND: Increasing evidence suggests that innate immune system may have a key role in the pathogenesis of the inflammatory bowel disease (IBD). Bactericidal/permeability increasing protein (BPI) has an important role in the recognition and neutralization of gram-negative bacteria by host innate immune system. The polymorphism on BPI gene called Lys216Glu is on the suspected list of IBD pathogenesis. METHODS: We studied the Lys216Glu polymorphism on BPI gene, in a Turkish IBD patient population. A total of 238 IBD patients; 116 Crohn's disease (CD) and 122 ulcerative colitis (UC), besides 197 healthy controls were included in this study. RESULTS: The Glu/Glu genotype and allele frequencies were found to be statistically higher compared to healthy control group not only in CD patients [P: 0.03, OR: 1.87 (CI 95% 1.02-3.42) and P: 0.00001 (OR: 2.07 CI 95% 1.47-2.91) respectively] but also in UC patients [P: 0.0002, OR: 2.71 (CI 95% 1.53-4.80) and P: 0.00002 (OR: 2.71 CI 95% 1.53-4.80) respectively]. CONCLUSIONS: BPI polymorphism (Lys216Glu) is associated both to CD and UC. Our findings differ from the two Western European studies; one without any association and the other indicating an association only with CD. Our study is the first one reporting a novel association between BPI gene mutation (Lys216Glu) and UC.