[Investigation of the Contribution of Autoantibodies to Clinical Diagnosis in Liver Pathologies and the Identification of Accompanying Autoimmune Diseases]. / Karaciger Patolojilerinde Otoantikorlarin Klinik Taniya Katkisinin ve Eslik Eden Otoimmün Hastaliklarin Tanimlanmasindaki Rolünün Arastirilmasi.

Autoantibodies are frequently detected in the presence of autoimmune liver diseases (ALD) [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)] and are widely used to classify the disease clinically. The aim of this study was to investigate the contribution of autoantibodies for the diagnosis of ALD and the identification of other accompanying systemic autoimmune rheumatic diseases (SARD). In addition, it was aimed to compare the results of indirect immunofluorescence (IIF) antinuclear antibody (ANA) patterns and extractable nuclear antigen (ENA) antibodies. A total of 593 patients, including 544 patients with high liver function tests from general surgery/gastroenterology clinics and 49 patients referred from internal medicine/rheumatology clinics to investigate ALD, were included in the study. HBsAg and anti-HCV test results of the patients were found to be negative. ANA, anti-mitochondrial antibody (AMA)/anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibody (ASMA), antineutrophil cytoplasmic antibody (ANCA) assays were performed by indirect immunofluorescence method (IIF) (Euroimmune AG, Luebeck, Germany). Extractable nuclear antigen (ENA) (nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, dsDNA, nucleosome, histone, ribosomal P-protein, AMA-M2, Ro-52, PM-Scl, CENP-B, PCNA, DFS70) and liver profiles [soluble liver antigen\liver pancreas antigen (SLA/LP), liver cytosolic antigen1(LC-1), LKM-1, anti-mitochondrial antibody M2(AMA-M2)] (Euroimmune AG, Luebeck, Germany) were detected by immunoblot (IB) method. Demographic characteristics, clinical data, presence of systemic autoimmune rheumatic diseases (SARD), radiological and laboratory findings were determined from the medical records. Autoantibody tests were found to be negative in 461 (77.7%) of 593 patients (mean age= 53.3 ± 15.6, age range= 18-90), and were positive in 132 (22.3%) (86.4% female) of the patients. Of the patients with positive autoantibodies, 60.6% (80/132) were diagnosed as PBS and 1.5% (2/132) were diagnosed as AIH (positive anti-LC-1 and anti-LKM1 antibodies). Fourteen of the patients (10.6%) with centromere, nuclear membrane (NM), multiple nuclear dot (MND) staining patterns and elevated liver enzymes could not be diagnosed as a specific disease and were followed up. PBS (13/30) was detected in approximately half of the patients diagnosed with SARD. The most common accompanying SARD in PBC patients was Sjögren's syndrome (SS) (7.5%, 6/80), followed by rheumatoid arthritis (RA) (5.0%, 4/80), scleroderma (2.5%, 2/80), and systemic lupus erythematosus (SLE) (1.3%, 1/80) respectively. The most common pattern was the AMA staining pattern (34.8%, 46/132) among the autoantibody positive patients. AMA and ANA staining patterns were detected together in 31.1% (41/132) of the patients. In the ENA profile results of these patients, the most common profile detected was anti-Ro-52 (65.9%, 27/41), followed by anti-SSA (34.1%, 14/41), anti-SSB (22.0%, 9/41) and anti-CENP-B (12.2%, 5/41) autoantibodies , respectively. ANA patterns were detected in 32.6% (43/132) of the patients (NM 9.1%, centromere 9.1%, MND 6.8%, respectively). In our study, 87.5% (70/80) of the patients diagnosed as PBS were found to have AMA positivity and 12.5% (10/80) of them had ANA positivity (such as NM, CNN, centromere). The characteristics, laboratory and radiological findings of the patients with isolated AMA positivity alone (Group 1) and patients with multiple patterns/autoantibodies (Group 2) were compared. In patients with multiple patterns/autoantibodies (Group 2), the presence of cirrhosis and liver heterogeneity were found to be higher than Group 1 (p= 0.049). ALD associated autoantibodies can be detected before years from the clinical disease. ALD may be associated with various SARD. Detection of ALD-related autoantibodies in patients diagnosed with SARD can provide early diagnosis of these patients. These autoantibodies guide both diagnosis and prognosis as in PBC. Collaboration between the laboratory specialist and the clinician is critical in the diagnosis, management and early recognition of these patients before clinical disease.

The Prevalence of Barrett Esophagus Diagnosed in the Second Endoscopy: A Retrospective, Observational Study at a Tertiary Center.

At present, we do not know the exact prevalence of Barrett esophagus (BE) developing later in patients without BE in their first endoscopic screening. The purpose of this study was to determine the prevalence of BE on the second endoscopic examination of patients who had no BE in their first endoscopic examination.The data of the patients older than 18 years who had undergone upper gastrointestinal system endoscopy more than once at the endoscopy unit of our clinic during the last 6 years were retrospectively analyzed.During the last 6 years, 44,936 patients had undergone at least one endoscopic examination. Among these patients, 2701 patients who had more than one endoscopic screening were included in the study. Of the patients, 1276 (47.3%) were females and 1425 (52.7%) were males, with an average age of 54.9 (18-94) years. BE was diagnosed in 18 (0.66%) of the patients who had no BE in the initial endoscopic examination. The patients with BE had reflux symptoms in their medical history and in both endoscopies, they revealed a higher prevalence of lower esophageal sphincter laxity, hiatal hernia, and reflux esophagitis when compared to patients without BE (P < 0.001).Our study showed that in patients receiving no diagnosis of BE on their first endoscopic examination performed for any reason, the prevalence of BE on their second endoscopy within 6 years was very low (0.66%).

Cirrhosis with ascites: Is the presence of hemorrhagic ascites an indicator of poor prognosis?

BACKGROUND/AIMS: Hemorrhagic ascites in patients with cirrhosis is described as a RBC (Red Blood cell) > 50,000/mm³ and leads to increased morbidity and mortality. Positive red blood cells at a level of less than 50,000/mm³ (10,000-50,000) may be encountered in the ascites but it is not known whether this is clinically significant or not. This study aimed to examine the outcome of hemorrhagic ascites in patients with advanced cirrhosis. MATERIALS AND METHODS: Data from 329 cirrhotic patients with ascites who received paracentesis at least once due to ascites was retrospectively analyzed from the period of 2007-2013 from the Türkiye Yüksek Ihtisas Hospital, Department of Gastroenterology. Patients were divided according to the number of RBC, with greater than 10,000/mm³ being described as hemorrhagic ascites, and less than 10,000/mm³ described as the normal or control group. Patient data included: number of accepted intensive unit service stays, acute kidney injury (AKI), hepatic encephalopathy (HES), model for end-liver disease (MELD) score, Child Pugh score (CPS), degree of esophageal varices, spleen size and mortality rates. RESULTS: Patients were defined as having hemorrhagic ascites with a RBC count greater than 10,000/mm³ in 118 (35.9%) patients and as a non-hemorrhagic ascites group with less than 10,000/mm³ in 211 (64.1%) patients. The hemorrhagic ascites group had advanced liver disease symptoms compared to the control group. Meld score in the hemorrhagic group was statistically higher than in the control group (21.5±8.3 vs. 17.3±6.6; p value: 0.001). The median value of bilirubin was 5.9 (0.45-33) in the hemorrhagic ascites group and 4.01 (0.39-33) in the non-hemorrhagic group (p value: 0.001). Using multivariate logistic regression analysis, hemorrhagic ascites was also an independent predictor of mortality (HR 2.7 1.4-6.3), with other mortality indicators being HCC (HR 3.1 1.5-6.4) and HRS (HR 2.6 1.2-5.5). CONCLUSION: Patients with hemorrhagic ascites had higher HRS, SBP and admissions to the intensive care unit. We believe that the presence of hemorrhagic ascites can be used as a marker for advanced liver disease and for predicting mortality.

Diverticulum With Papillae: Does Position of Papilla Affect Technical Success?

BASIS AND PURPOSE: The presence of peripapillary diverticulum (PPD) can cause some biliary diseases, especially common bile duct stones, and also, literally, can change the technique of endoscopic retrograde cholangiopancreatography (ERCP) and affect the complication ratio of this procedure. In this study, we investigate the effect of localization and position of the papilla according to the diverticulum on the success of therapeutic ERCP procedures. MATERIALS AND METHODS: The study was conducted prospectively in the patients with naive papillae, who underwent ERCP for a period of 16 months. In all patients, the position of papillae according to the diverticulum (the periphery of the diverticulum is thought as the clock circumference, and the position of papillae is defined as the dials of clock), the success rate of biliary cannulation, total procedure time, overall treatment success rate of ERCP, and the complications are investigated. RESULTS: During this period, 222 (18.5%) of the 1205 enrolled patients who underwent ERCP had PPD. Of the patients with PPD, 123 (55.4%) were female and 99 (44.6%) were male, and the median age was 68.9±10.1 years. According to the position of the papilla by the diverticulum, 90 (40.5%) patients have it on 7 o'clock position, 64 (28.8%) patients have on 6 o'clock position, 63 (28.3%) patients have on 5 o'clock position, and 5 (2.3%) patients have on 1 o'clock position. In the cases of the papilla on 1 o'clock position according to the diverticulum, cannulation procedures were found to be more difficult than other patients (P<0.05). The presence of the diverticulum did not affect the success of therapeutic procedures and did not increase the ratio of complications. CONCLUSIONS: In the presence of PPD, additional cannulation techniques may be required for the procedure. Particularly, the aid of percutaneous techniques may be needed for the papilla on 1 o'clock position.

Nitric oxide is a potential mediator of hepatic inflammation and fibrogenesis in autoimmune hepatitis.

BACKGROUND: Despite advances in the understanding of the pathophysiological basis of autoimmune hepatitis (AIH), it is still difficult to delineate the mechanisms involved in progression from hepatic inflammation toward fibrosis. Our aim was to study serum concentrations of NO in AIH of different histological severity and possible effects of immunosuppressive therapy on NO production. MATERIALS AND METHODS: We studied serum NO metabolites (NOx) in 47 consecutive patients with AIH and in 28 age- and sex-matched controls. RESULTS: Serum NOx concentrations were higher in AIH patients than in controls (10.3 (4.5-27.3 µmol/L) vs. 4.3 (1.6-14.3 µmol/L), p < 0.001). According to liver histology, median NOx concentrations were significantly higher in patients with severe interface hepatitis compared to patients with mild-moderate interface hepatitis (12.3 (4.5-27.3 µmol/L) vs. 9.3 (4.6-20.3 µmol/L), p = 0.029). Similarly, serum NOx concentrations were significantly higher in patients with advanced fibrosis than in those with early fibrosis (12.2 (4.6-27.3 µmol/L) vs. 9.3 (6.6-12.8 µmol/L), p = 0.018). NOx concentrations decreased in 16 AIH patients who were tested also after biochemical remission was achieved (12.6 (4.5-22.8 µmol/L) at baseline and 5.9 (2.8-10.5 µmol/L) after remission, p = 0.001). CONCLUSION: This study shows that serum NOx levels are associated with the histological severity of AIH. Hepatocyte inflammation and injury may activate hepatic stellate cells and kupffer cells, and the consequences may include release of NO, which ultimately promotes hepatic fibrosis. Immunosuppressive therapy inhibits this process and the production of NO.

The change in microorganisms reproducing in bile and blood culture and antibiotic susceptibility over the years.

BACKGROUND/AIMS: Infection in the bile tract is a major cause of bacteremia and is related to high morbidity and mortality. We examined the changes in bacteria types and antibiotic susceptibility in bile cultures and simultaneous blood cultures taken from patients who applied for endoscopic retrograde cholangio pancreatography (ERCP)/percutaneous transhepatic cholangiography (PTC) for different bile duct diseases in recent years. MATERIALS AND METHODS: Bacteria types that reproduce in bile and blood cultures from patients who applied for ERCP/PTC between the years of 2007 and 2012 in our clinic were examined. All patients were evaluated together, and in addition, the periods between 2007 and 2009 (Group 1) and between 2010 and 2012 (Group 2) were compared. RESULTS: In total, 550 patients applied to this study. There were 266 patients in Group 1 and 284 in Group 2. Reproduction occurred in 77.6% of bile cultures. In the order of frequency, these cultures consisted of Escherichia coli (32.8%), Enterococcus spp. (26.2%), and Pseudomonas aeruginosa (11%). Enterococcus spp. were determined to be higher in Group 2 than Group 1 (p<0.016). Resistance to quinolones was found in 74.1% of patients, to ampicillin in 73.2%, and to cephalosporins in an average of 61%. Vancomycin was the most susceptible antibiotic (93.4%) to gram-positives. Resistance to piperacillin-tazobactam and amikacin was higher in Group 2 than Group 1 (p=0.001 and p=0.003, respectively). CONCLUSION: The most frequently reproducing bacteria in the bile cultures evaluated in our hospital were Escherichia coli and Enterococcus spp. Although it was thought that the antibiotics given empirically were effective against these bacteria, there was resistancerate of 75% in our study. We determined that the first- and second-step treatment protocols must be updated.

Low magnification narrow band imaging by inexperienced endoscopists has a high accuracy in differentiation of colon polyp histology.

BACKGROUND/OBJECTIVE: Several studies have shown that NBI can predict the colorectal polyp histology with moderate to high accuracy. Most of them were conducted by highly experienced endoscopists at academic centers by using high magnification colonoscopes. We evaluated the accuracy of standard definition low magnification NBI in predicting the real time histology of colorectal polyps when used by inexperienced endoscopists and whether it can meet the thresholds recently defined for discard, resect and discard strategies of diminutive polyps by ASGE. METHODS: The study was a prospective observational trial and involved 430 patients who underwent colonoscopy. A total of 214 polyps were detected in 317 patients. Colonoscopies were performed by a gastroenterology attending physician and two fellows who had no experience in NBI. Standard definition low magnification colonoscopes were used. The endoscopists recorded the size, Paris classification, and location of polyps under white light and consecutively described the superficial mucosal architecture and vascular pattern based on NBI International Colorectal Endoscopic criteria. RESULTS: The overall accuracy of NBI in predicting adenomatous histology was 93.4%. The negative predictive value for diagnosing adenomatous histology in diminutive rectosigmoid polyps (93.3%) and the accuracy in predicting the colonoscopy surveillance interval (92.3%) were above the threshold levels defined by ASGE. CONCLUSIONS: Low magnification NBI by inexperienced endoscopists has a high accuracy in predicting in vivo colorectal polyp histology encouraging its use in routine clinical practice.

A simple method to improve adenoma detection rate during colonoscopy: altering patient position.

BACKGROUND: Colonoscopy is currently considered to be the gold standard method for detecting and removing adenomatous polyps. However, tandem colonoscopy studies reveal a pooled polyp miss rate of 22%. OBJECTIVE: A prospective randomized trial was conducted to assess whether alteration of patient position during colonoscopy withdrawal increases the adenoma detection rate (ADR). METHOD: The study group included 120 patients who presented for elective colonoscopic examination. After reaching the cecum, patients were randomly assigned in a 1:1 ratio to examination in either the left lateral position or other positions (left lateral position for the cecum, ascending colon and hepatic flexure; supine for transverse colon; and supine and right lateral position for splenic flexure, descending and sigmoid colon) first. Examination of the colon was performed segment by segment. The size, morphology and location of all polyps were recorded. Polyps were removed immediately after examination of a colon segment when all positions were completed. ADR and polyp detection rates (PDR) were calculated. RESULTS: A total of 102 patients completed the study. Examination in the left lateral position revealed 66 polyps in 31 patients (PDR 30.3%) and 42 adenomas in 24 patients (ADR 23.5%). PDR increased to 43.1% (81 polyps in 44 patients) and the ADR to 33.3% (53 adenomas in 34 patients) after the colon was examined in the additional positions (P<0.001 and P=0.002, respectively). The increase in the number of adenomas detected was statistically significant in the transverse and sigmoid colon. The addition of position changes led to a 9.8% increase in the ADR in the transverse colon, splenic flexure, and descending and sigmoid colon. The frequency of surveillance interval was shortened in nine (8.8%) patients after examination of the colon in dynamic positions. CONCLUSION: Alteration of patient position during colonoscopy withdrawal is a simple and effective method to improve ADR.