Human Leucocyte Antigen Genotyping in Celiac Disease: Reasons for Inappropriate Use.

BACKGROUND: Celiac disease (CD) is an autoimmune enteropathy, which may need further Human Leukocyte Antigen (HLA) testing beyond autoantibodies for diagnosis due to the necessity of lifetime gluten restriction. HLA genotyping test is useful in certain scenarios for CD diagnosis and screening. The aim of this study was to evaluate the reasons for inappropriate requesting of HLA testing. METHODS: One hundred and fifteen patients, who had been tested for CD-related HLAs, were included in this study. Final diagnosis, indication of HLA test, serological and histopathological findings were re-evaluated to determine the inappropriate usage of HLA testing. RESULTS: Among all patients, 44 (38.2%) were diagnosed with CD according to their genotyping results. The frequency of DQ 2.5, DQ8 and DQ2.2 haplotypes among these patients was 57.2%, 28.2%, and 14.3%, respectively. HLA test was performed inappropriately in 35 (30.4%) of patients. The most common reason was serology and pathological findings of patients were already conclusive as CD in 15 (42.9%) patients. Serology negative patients were tested without any supporting finding of CD in 11 (31.4%) patients. Last identified reason was that patients whose serology and intestinal biopsy were not conclusive as CD in 9 (25.7%) patients. CONCLUSIONS: Before requesting HLA typing test, patient's data should be thoroughly evaluated to confirm the need for test.

Treatment Response and Outcome with Two Different Prednisolone Regimens in Autoimmune Hepatitis.

BACKGROUND: Beyond available guidelines, therapy of autoimmune hepatitis (AIH) shows wide variation among physicians. We compared two regimens for treatment naive AIH: one recommended protocol with an initial prednisolone dose of 30 mg/day and our own 40 mg/day prednisolone with a slow dose tapering protocol. We analyzed the safety, response rates, and outcomes for two groups of treated patients. PATIENTS AND METHODS: We retrospectively evaluated data of 71 AIH patients including, group I (n = 32, prednisone 30 mg/day) and group II (n = 39, prednisone 40 mg/day). All patients also received azathioprine. RESULTS: The frequency of complete biochemical response was significantly higher in group II than in group I (69.2 vs. 43.8%, p = 0.031) after 3 months of therapy, but not after 6 and 12 months (79.5 vs. 59.4%, p = 0.065 and 89.5 vs. 80.6%, p = 0.30). In patients with severe interface hepatitis, the complete response rates were significantly higher in group II than in group I after 3 (63.6 vs. 23.1%, p = 0.02) and 6 months (72.7 vs. 38.5%, p = 0.046), but not after 12 months of therapy (86.4 vs. 69.2%, p = 0.221). Relapses were observed in 50% of group I and in 35.9% of group II during maintenance therapy (p = 0.23). Overall survival was significantly better in group II than in group I (100 vs. 87.5%, log-rank, p = 0.048). No severe steroid-related side effects were observed in either group. CONCLUSIONS: Our real-world experience suggests that an initial prednisolone dose of 40 mg/day with a slower tapering protocol induces earlier biochemical response, tends to result in less relapses during maintenance, and is associated with a better disease outcome.

Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Patients with Autoimmune Hepatitis.

BACKGROUND/AIMS: The performance of non-invasive fibrosis markers has not been well studied in autoimmune hepatitis (AIH). Acoustic radiation force impulse imaging (ARFI) is a non-invasive radiological method for assessment of liver fibrosis. The aim of this study was to evaluate the accuracy of ARFI for fibrosis staging in patients with AIH. METHODOLOGY: AIH patients who undergone for control liver biopsy after at least two years of biochemical remission period were also assessed by ARFI. Liver fibrosis was staged according to the METAVIR scoring system. RESULTS: A total of 15 patients (13 women and 2 men) with mean age of 40.9 (18-59 years) were included in the study. Repeat liver biopsy was performed a mean of 4.9 (3-9 years) after AIH diagnosis. Nine patients had significant fibrosis scores (F ≥ 2) while, remain 6 patients had mild or no fibrosis. The mean (±SD) shear wave velocities for patients with fibrosis stage II-IV was significantly higher than those with fibrosis stage 0-I (2.28 ± 0.68 m/s and 1.20 ± 0.24, respectively, p = 0.002). CONCLUSIONS: ARFI is able to differentiate significant from non significant liver fibrosis in patients with AIH. Our study suggests that this non-invasive method can be used for monitoring fibrosis progression in AIH.

Effect of Connective Tissue Manipulation on Symptoms and Quality of Life in Patients With Chronic Constipation: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to examine the effects of connective tissue manipulation (CTM) on the severity of constipation and health-related quality of life in individuals diagnosed with chronic constipation. METHODS: Fifty patients with a diagnosis of chronic constipation according to Rome III criteria were recruited and randomized to an intervention (n = 25) or control group (n = 25). The intervention group received CTM in addition to the lifestyle advice, whereas the control group was given only lifestyle advice for constipation. All assessments were performed at baseline and at the end of 4 weeks. The primary outcome measure was the Constipation Severity Instrument. Secondary outcomes included Patient Assessment of Constipation Quality of Life Questionnaire, Bristol Stool Scale, and 7-day bowel diary. Differences between groups were analyzed with t tests, Mann-Whitney U test and χ(2) test. RESULTS: Compared with the control group, subjects in the intervention group reported significantly greater improvement in total and subscale scores of the Constipation Severity Instrument and Patient Assessment of Constipation Quality of Life Questionnaire (P < .05). Based on the results from bowel diaries, the improvements in the number of bowel movements, duration of defecation, stool consistency, and the feeling of incomplete evacuation in the intervention group were also significantly more than the control group (P < .05). CONCLUSION: This study showed that CTM and lifestyle advice were superior to reducing symptoms of constipation and quality of life compared with lifestyle advice alone for patients with chronic constipation.

Factors associated with response to therapy and outcome of patients with primary biliary cirrhosis with features of autoimmune hepatitis.

BACKGROUND & AIMS: For patients with primary biliary cirrhosis (PBC) with features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid (UDCA) alone or in combination with immunosuppression is controversial. Little is known about the factors associated with initial response to therapy or outcome. We performed a retrospective analysis of treatment strategies and factors associated with outcomes of patients with PBC-AIH. METHODS: We analyzed data from 88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7 centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a combination of UDCA and immunosuppression (n = 58). RESULTS: Of patients who received UDCA alone as the first-line therapy, 37% did not respond to treatment. Severe interface hepatitis was independently associated with lack of response to treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The combination of UDCA and immunosuppression was effective in 73% of patients who had not been previously treated or had not responded to UDCA. The presence of advanced fibrosis was associated with lack of response to the combination of UDCA and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03-0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and mycophenolate mofetil) led to biochemical remission in 54% of patients who did not respond to initial immunosuppression. Liver transplants were given to 4 patients with PBC-AIH. Five patients died during follow-up (3 from liver-related causes). CONCLUSIONS: In a retrospective study of a large cohort of patients with PBC-AIH, UDCA alone did not produce a biochemical response in most patients with severe interface hepatitis; these patients require additional therapy with immunosuppression. Second-line immunosuppressive agents are effective in controlling disease activity in patients who do not respond to conventional immunosuppression.

Low serum vitamin D levels are associated with severe histological features and poor response to therapy in patients with autoimmune hepatitis.

BACKGROUND AND AIM: 25-Hydroxyvitamin D [25(OH)D] has an important role in fibrosis progression and inflammatory response in patients with various etiologies of chronic liver disease. However, its influence on autoimmune hepatitis (AIH) has not been investigated. We evaluated the association of serum 25(OH)D levels with clinical, biochemical and histological features and response to therapy in AIH. MATERIALS AND METHODS: Serum 25(OH)D levels were quantified in 68 therapy naïve AIH patients and 34 healthy controls. RESULTS: Mean serum 25(OH)D levels were significantly lower in AIH compared to healthy controls (16.8 ± 9.2 vs. 35.7 ± 13.6, p < 0.0001). Low levels of 25(OH)D (<30 µg/L) were independently associated with advance fibrosis and severe interface hepatitis in AIH patients [p = 0.014; odds ratio (OR) 0.12, 95% confidence interval (CI) 0.02-0.65 and p = 0.020; OR 0.17, 95% CI 0.04-0.76, respectively]. Severe 25(OH)D deficiency (<10 µg/L) was associated with advance fibrosis, severe interface hepatitis, low platelet counts and sampling time in a univariate analysis. Only interface hepatitis and fibrosis scores were independently associated with 25(OH)D deficiency in a multiple regression analysis (p = 0.005; OR 0.12, 95% CI 0.03-0.53 and p = 0.022; OR 0.15, 95% CI 0.03-0.75, respectively). Mean serum 25(OH)D levels were lower in non-responders compared to responders (9.2 ± 4.8 vs. 17.1 ± 9.4, p = 0.015), and 25(OH)D deficiency was more commonly observed in non-responders than the responders (80 vs. 43%, p = 0.036). CONCLUSIONS: Low 25(OH)D levels are associated with advance fibrosis and severe inflammation in AIH. Our study suggests that vitamin D may be a potential biomarker that predicts response to therapy and histological features in AIH.

Long-term follow-up study in Budd-Chiari syndrome: single-center experience in 22 years.

GOALS: We aimed to present our long-term surveillance experience in patients with Budd-Chiari syndrome (BCS), and we retrospectively evaluated the natural history, results of thrombophilia studies, and the factors related to mortality. BACKGROUND: Primary BCS is a rare form of vascular disease, secondary to underlying thrombophilia. Because of its rarity and heterogeneous nature, there is a scarcity of knowledge about the natural history of the disease. STUDY AND RESULTS: In 22 years, a total of 62 patients with primary BCS were followed in our tertiary hospital. We identified an acquired cause of BCS in 40 out of 62 patients (64.5%), whereas in 6 patients (9.7%), we found no identifiable cause. One or more thrombophilia causes were identified in 56 patients (90.3%). In 19 patients with myeloproliferative disease, 15 had Janus tyrosine kinase 2 mutation analysis and Janus tyrosine kinase 2 positivity was found in 10 patients. In regression analysis, portal vein thrombosis was found to be the only indicator of mortality, with an estimated instantaneous risk of 8.4. CONCLUSIONS: In this study, we present one of the largest series of BCS in the English literature. We have shown that the multifactorial nature of underlying thrombophilia should be thoroughly investigated. In a patient with BCS, a clinician should be alert for the development or coexistence of portal vein thrombosis due to its deleterious effect on mortality.

The DETAIL questionnaire is a useful and effective tool to assess spondyloarthritis in patients with inflammatory bowel disease.

Introduction: This study aimed to determine the effectiveness of adding a simple questionnaire related to musculoskeletal system to routine outpatient examination to detect undiagnosed axial and peripheral arthropathy in patients with inflammatory bowel disease (IBD). Materials and methods: A musculoskeletal symptom questionnaire was given to all patients with IBD during their follow-up examinations between January 2020 and November 2021. The DETAIL questionnaire consisting of six questions about the musculoskeletal system was administered by asking the patients with IBD. All patients who answered yes to at least one of these questions were directed to specialists in the rheumatology department to undergo a detailed examination. The patients who were diagnosed with rheumatological disease after further investigation were recorded. Patients with a known diagnosis of rheumatological disease were excluded from the study. Findings: There were 333 patients with IBD included in the study. Of these patients, 41 (12.3%) had a previously diagnosed rheumatological disease and were excluded from the evaluation. Of the remaining 292 patients (147 with ulcerative colitis, 139 with Crohn's disease and six with indeterminate colitis; mean age 42 years), 67 (23%) answered yes to at least one of the questions and were referred to a rheumatology consultation. Rheumatological examination was completed in 52 patients. As a result of the evaluations, 24 patients (8.2%) were diagnosed with enteropathic arthritis (14 axial, 9 peripheral, and 1 axial plus peripheral). Patients with newly diagnosed enteropathy had a lower median disease age than patients without enteropathy. Conclusion: The DETAIL questionnaire is an effective and easy tool for identifying missed cases of SpA in patients with IBD.

Risk of Bleeding After Percutaneous Endoscopic Gastrostomy in Patients Using Antithrombotic Drugs.

BACKGROUND: The rate of using antithrombotic (AT) drugs is frequently high in patients who require percutaneous endoscopic gastrostomy (PEG). The aim of this study was to determine whether the risk of bleeding after PEG increases in patients whose AT drugs were discontinued according to the European Society Gastrointestinal Endoscopy guidelines (warfarin for 5 d, low molecular weight heparin for 24 h, DOAC for 3 d, and clopidogrel for 7 d). PATIENTS AND METHODS: Data from 243 patients, who underwent PEG tube placement and received AT drugs and 206 patients who did not between 2018 and 2021 in our hospital, were evaluated retrospectively. Bleeding was defined as requiring blood transfusion, hematemesis and/or melena, decreased hemoglobin, or bleeding from PEG. RESULTS: A total of 243 (54.1%) patients (121 (49.7%), women, mean age (75.7 y) who underwent PEG and received AT drugs, and 206 (45.9%) patients who did not (92 (44.6%), women, mean age (63.15 y). The medications and bleeding rates of the patients are given in Table 1. The rate of bleeding in patients using AT medication was significantly higher than that in patients not using medication (Table 2) ( P = 0.007). When the AT drugs were compared among themselves, the bleeding risk did not differ. Bleeding was detected in 10 patients with bleeding from the PEG tube in 4 with melena. Bleeding detected in 14 patients was controlled with adrenaline injections. None of the patients required transfusion or repeat endoscopies. No bleeding-related deaths were reported. CONCLUSION: Even if patients receiving AT drugs are treated as recommended by international guidelines, it should be kept in mind that bleeding may occur after PEG, and the patients should be followed accordingly.

Small Bowel Video Capsule Endoscopy Guidance in Practice: Expert Opinion Report.

Capsule endoscopy, in clinical use since the 2000s, has disrupted the diagnosis of various small bowel diseases, especially obscuregastrointestinal bleeding. An overview of information on indications, contraindications, patient management, and patient preparationfor capsule endoscopy, which allows the evaluation of the entire gastrointestinal tract, will be helpful for both referrers and capsuleendoscopy. This review critically considers current evidence on the optimal clinical use of capsule endoscopy and addresses areas in the "gray zone."

Red cell distribution width can predict intestinal atrophy in selected patients with celiac disease.

BACKGROUND: Red cell distribution width (RDW) has been shown as a distinctive marker of mortality and morbidity in a wide spectrum of conditions related to systemic inflammation or deficiency of antioxidant nutrients. OBJECTIVE: We aimed to investigate the predictive value of RDW in detection of intestinal atrophy in celiac disease (CD). METHODS: Iron indices and RDW were studied in 49 patients with CD to evaluate the utilization of RDW as a predictive marker for presence of intestinal atrophy. RESULTS: Sixty-nine percent of patients had iron deficiency at initial presentation and 89% had abnormal RDW defined as >14. Receiver operating characteristics curves of RDW has been found to be a predictive of intestinal atrophy at levels higher than 17.25 (68% sensitivity and 85% specificity). In patients with transglutaminase antibody IgA titers >200 U/l, RDW level >17.75 showed 76% sensitivity and 100% specificity for intestinal atrophy. CONCLUSIONS: We suggest that RDW can be used as a surrogate marker of atrophy in patients with iron deficiency and suspected CD. In addition, the sensitivity, specificity, negative and positive predictive values of RDW increases when used in combination with high levels of transglutaminase IgA antibody.

The impact of COVID-19 disease on the natural course of cirrhosis: Before and after starting vaccination.

Background: Cirrhosis has been reported as an important risk factor for death in coronavirus disease 2019 (COVID-19) disease. In this study, we aimed to investigate the effects of COVID-19 on the natural course of cirrhosis before and after starting vaccination. Methods: The cirrhosis patients in our cohort (n: 140; median age:56; 71 female) were included in this study. The median MELD (Model For End-stage Liver Disease) score was 11 (6-25) and CCI (Charlson Comorbidity Index) score was 4 (1-11). In total, 85 had CTP (Child-Turcotte-Pugh)-A, 44 had CTP-B and 11 had CTP-C cirrhosis. The course of COVID-19 in this patient group was evaluated before and after COVID-19 vaccination. Results: Between March 2020 and January 2021, 36 of the 140 cirrhosis patients had developed COVID-19. Cirrhosis (+)/COVID-19 (+) and Cirrhosis (+)/COVID-19 (-) groups did not differ in terms of age, CCI and MELD-Na scores, or gender. There were six deaths in the Cirrhosis (+)/COVID-19 (+) group and five in the Cirrhosis (+)/COVID-19 (-) group [6/36 (16.6%) vs. 5/104 (4.8%); p: 0.03]. Patients who died were older, had higher CCI and MELD-Na scores, and lower albumin levels. Having had COVID-19 [6.45 (1.43-29.4); p: 0.015], higher MELD-Na score [1.35 (1.18-1.60); p: 0.001] and higher CCI score [1.65 (1.14-2.39); p: 0.008] were found to be independent predictors of mortality. After effective vaccination started in Turkey, only 11 of the remaining 129 patients developed COVID-19, and only one patient died, who was unvaccinated. Discussion: In our cirrhotic cohort, COVID-19 disease was associated with 16% mortality in the pre-vaccination period. COVID-19 vaccination prevents serious illness and death due to COVID-19 in cirrhotic patients.

Investigation of Dientamoeba fragilis and Blastocystis in patients from Turkey with ulcerative colitis and irritable bowel syndrome: Any relation with genotypes?

Blastocystis sp. and Dientamoeba fragilis are two most common protists worldwide, whose pathogenic potentials are a matter of debate since their discovery. This study aims to investigate the relationship between the activation of ulcerative colitis (UC) and irritable bowel syndrome (IBS) with these protists. A total of 100 patients (35 IBS, 35 active UC, and 30 remittent UC), diagnosed at Hacettepe University Adult Hospital (Ankara, Turkey), were screened for D. fragilis and Blastocystis sp. with microscopic examination using the methods of wet mount, trichrome staining, conventional PCR, nested PCR, real-time PCR and genotyping. Eight patients (4 IBS, 2 active, and 2 remittent UC patients) were found to be D. fragilis positive. 18S rRNA region of the parasite was amplified in four of the patients, whereas cathepsin L-like cysteine peptidase; clan Sc, family S9, serine peptidase; and clan MH, family M20 metallopeptidase in six different patients. All isolates were Genotype 1. Sequence results showed very limited diversity. A total of nine patients (3 IBS, 5 active UC, 1 remittent UC) were found to be positive for Blastocystis sp., all of which were Subtype 3. One active UC and one IBS patient were found to be positive for both parasites. No statistically significant difference was detected between the patient groups in means of parasite detection. D. fragilis was found to be related to older age (p=0,045). In our study, no significant correlation was identified between D. fragilis and Blastocystis sp., and the activation of UC and IBS. More studies are needed on the host-parasite relationship, including the role of gut microbiota, together with transcriptomic and metabolomic assessments to unveil the pathogenicity of both protists.

Clinical and Endoscopic Consequences of Delay in Stent Exchange Procedures With ERCP During the Covid-19 Pandemic.

INTRODUCTION: During the COVID-19 pandemic, elective endoscopic retrograde cholangiopancreatography (ERCP) procedures have been postponed as recommended by international guidelines. In this study, the results of biliary and pancreatic ERCP procedures that had to be postponed during the pandemic process were investigated. MATERIALS AND METHODS: Forty-seven patients whose stent exchange procedures with ERCP were postponed between March 2020 and June 2020 due to the COVID-19 pandemic were included in the study. Patients were evaluated in 2 groups as delayed biliary procedures (n: 32) and delayed pancreatic procedures (n: 15). Clinical problems (biliary or pancreatic pain, itching, cholangitis, etc.) and technical problems encountered during the procedure (stent migration, abundant stone sludge in the bile ducts, etc.) were compared with 46 patients who could be treated without delay (39 interventions for the biliary system and seven interventions for the pancreas). FINDINGS: Considering the procedures for the biliary system, there was no difference in age and sex between the groups. Although clinical problems in biliary procedures were more common in the group with delay than in those without delay, this difference was not significant (34% vs. 20%; P : 0.14). The technical problems encountered during the procedures in the group with delay were significantly higher than those without delay (21% vs. 2.5%; P : 0.019), with stent migration being the most common problem (n: 5). Age and sex did not differ in the patients who had pancreatic interventions with and without delay. The clinical problems that developed in the patients did not differ between the groups with and without delay (26% vs. 28%; P : 0.8). Although technical problems were encountered in 1 out of 15 patients in the group with delay, no technical problem was experienced in the group without delay ( P : 0.68). CONCLUSION: Postponing elective ERCP procedures for the biliary system not for the pancreatic system during the COVID-19 pandemic brings technical problems.