Prevalence and predictors of metabolic-associated fatty liver disease in liver transplant recipients: A cross-sectional prospective study.

Background and Aim: Metabolic-associated fatty liver disease (MAFLD) has emerged as a significant global health concern. However, the prevalence and predictors of MAFLD in post-liver transplantation (LT) patients remain uncertain. This study aimed to determine the prevalence and predictors of MAFLD in LT recipients and to assess the effectiveness of controlled attenuation parameter (CAP) values in diagnosing post-transplant MAFLD. Materials and Methods: A cross-sectional prospective study was conducted involving 128 adult patients who had undergone LT, and had received liver imaging, and vibration-controlled transient elastography (VCTE). MAFLD was diagnosed on the basis of the presence of liver steatosis detected through imaging and specific metabolic risk abnormalities. Results: The prevalence of MAFLD after LT was 34.4%, with 22.1% categorized as de novo MAFLD, and 12.3% as recurrent MAFLD. Posttransplant diabetes (OR: 4.88; 95% CI 1.30-18.34; p=0.019) and higher CAP values (OR: 1.04; 95% CI 1.02-1.06; p=0000) were identified as independent predictors of post-LT MAFLD. A CAP cutoff value of 270 dB/m exhibited an area under the receiver operating curve of 0.84 in detecting MAFLD. Conclusion: These findings underscore the notable prevalence of MAFLD in liver transplant recipients and suggest the potential utility of VCTE as a non-invasive tool for its detection.

The Role of Self-Expandable Metallic Stents in the Treatment of Malignant Strictures in all Segments of the Gastrointestinal Tract.

Objectives: Management of malignant gastrointestinal (GI) obstruction presents a significant challenge. Most patients are in a profoundly decompensated state due to underlying malignancy and are not ideal candidates for invasive surgical procedures. Self-expandable metallic stents (SEMSs) are used to provide permanent or temporary patency in all endoscopically accessible stenosis of the GI tract. In this study, it is aimed to analyse the characteristics and the efficacy of patients with malignant stenosis treated with SEMS, in all segments of the GI tract. Material and Methods: The sample consisted of 60 patients who underwent SEMS replacement, between 10 March 2014 and 16 December 2020, to treat malignant-related strictures in the GI tract at the Gastroenterology Department of the Health Sciences University Umraniye Training and Research Hospital. The data of the patients, hospital data processing database and electronic endoscopic database records were retrospectively scanned and recorded. The general characteristics of the patients and the treatment-related features were analysed. Results: The mean age of patients who were placed SEMS was 69.7 ± 13.7 years. Uncovered (15%, n: 9), fully covered (13.3%, n: 8), or partially covered (71.6%, n: 43) SEMS were successfully placed in all patients. Clinical success in patients with SEMS was 85.7% in the esophagus, 100% in the small intestine and 90.9% in the stomach and colon. About 11.4% migration, 14.2% pain, 11.4% overgrowth and 5.7% ingrowth were detected in patients who had SEMS placed in the oesophagus. Pain was detected in 9.1% and ingrowth in 18.2% of patients who had SEMS placed in the stomach. Pain was detected in 18.2% of the patients who had SEMS placed in the colon and migration was found in 9.1%. Conclusion: SEMS implant is a minimally invasive effective method in the palliative treatment of malignant strictures of the GI tract.

Post-ERCP Complication Analysis of an Experienced Center.

BACKGROUND/AIM: Post-ERCP pancreatitis (PEP), post-sphincterotomy bleeding (PSB), and Post-ERCP perforation are the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Identification of risk factors for post-ERCP complications is critical for postoperative follow-up. This study aimed to evaluate the most common post-ERCP complication risk factors in an experienced center. METHODS/DESIGN: The sample consisted of 1288 patients with naive papillae. Demographic characteristics, patient-related risk factors, procedure-related risk factors and postoperative complications were recorded. RESULTS: Patients had a mean age of 61.5±18.4 years. The prevalence of PEP, PSB, and post-ERCP perforation was 7.9%, 11.9%, and 0.5%, respectively. Among patient-related factors, female sex (OR 1.672 95% Cl 1.046 to 2.672) and narrowing of the choledochal diameter (OR 2.910 95% Cl 1.830 to 4.626) were associated with PEP. From procedure-related factors; precut sphincterotomy (OR 2.172 95% Cl 1.182 to 3.994), difficult cannulation (OR 5.110 95% Cl 2.731 to 9.560), pancreatic cannulation (OR 5.692 95% Cl 0.994 to 32.602) and postprocedure residual stone (OR 2.252 95% Cl 1.403 to 3.614) were found to be associated with PEP. The successful procedure (OR 0.378 95% Cl 0.204 to 0.699) had a protective effect on PEP. Choledocholithiasis indication (OR 3.594 95% Cl 1.444 to 8.942) and small papilla (OR 2.042 95% Cl 1.170 to 3.562) were associated with the development of PSB. Choledochal stenosis, periampullary-diverticulum, oral anticoagulant, and oral antiaggregant use were not associated with the development of PSB. Of the patients with post-ERCP perforation, 85.7% had difficult cannulation, 57.1% had precut sphincterotomy, and 28.6% had periampullary-diverticulum. CONCLUSION: Female sex, biliary stricture, precut sphincterotomy, difficult cannulation, pancreatic cannulation, and postoperative residual stone were associated with PEP. Choledocholithiasis indication and the presence of small papilla were associated with PSB.

EUS-FNA and ROSE in solid lesions of the pancreas; have the same diagnostic efficacy compared to pancreatic sites?

OBJECTIVE: Various techniques, needle types, and additional methods such as on-site pathological evaluation (ROSE) are used to increase the sensitivity of endoscopic ultrasound-fine needle aspiration (EUS-FNA), which is used in the diagnosis of pancreatic solid lesions. In this study, diagnosticity of the lesions according to the regions of the pancreas with EUS-FNA and ROSE performed with the slow pull technique using a 22 G needle will be evaluated. METHODS: A total of 82 patients who underwent EUS-FNA between January 2, 2015, and March 14, 2020, were included in the study. General and clinical information of the patients were recorded retrospectively. The patients were diagnosed according to The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology Classification. If the diagnosis could not be made with EUS-FNA and ROSE, the diagnosis was made with alternative methods of surgery or percutaneous biopsy. Patients diagnosed as benign with EUS-FNA and ROSE were followed for at least 1 year and were accepted as benign. RESULTS: The mean age of the patients was 63.2±10.5 years and 54 (69.6%) of them were male. The mean lesion size was 36.8 mm and the number of needle passes was 2.87. The overall sensitivity was 82.9% and the specificity was 100%. The sensitivity of EUS-FNA and ROSE in solid lesions in the head and body of the pancreas was higher than in lesions in the tail region (p=0.024). CONCLUSION: EUS-FNA and ROSE are an effective method in the diagnosis of pancreatic solid lesions. The use of a 22 G needle may be more diagnostic in the head and body of the pancreas than in the tail region.

Portal vein thrombosis risk factors in liver transplant candidates.

Background and Aim: Portal vein thrombosis (PVT) is particularly detected in advanced liver cirrhosis patients. We aimed to analyze the risk factors for PVT in liver transplant candidates. Materials and Methods: Dataset for consecutive 165 cirrhotic patients who were evaluated for liver transplantation (LT) were retrospectively analyzed. We sorted patients into two groups: patients with PVT and patients without PVT. Included variables were age, sex, etiology of liver disease, body mass index, MELD-Na score, Child-Pugh score, clinical variables reflecting portal hypertension, and hepatocellular carcinoma. Univariate and multivariate logistic regression analyses were used to identify risk factors of PVT. Results: Of 165 LT candidates, 46 had PVT (27.9%). Ascites, thrombocytopenia, history of variceal bleeding, and band ligation were risk factors for PVT in univariate analysis. In multivariate analysis, only a history of variceal bleeding (OR 3.45, 95% CI 1.02-11.6, p=0.046) significantly increased the risk of PVT. Conclusion: The previous history of variceal bleeding predicts PVT development in cirrhosis, suggesting that the severity of portal hypertension is a major predictive factor for PVT in patients with cirrhosis. Future prospective studies are needed to risk stratifying cirrhosis patients prior to LT for future PVT development and to define the prophylactic role of anticoagulation in these patients.

Validation of the PAGE-B score to predict hepatocellular carcinoma risk in caucasian chronic hepatitis B patients on treatment.

BACKGROUND: Several risk scores have been developed to predict hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. The majority of risk scores are based on pretreatment variables that are no longer considered risk factors for HCC development due to the suppression of hepatitis B virus replication early in the course of potent antiviral treatment in most patients. The PAGE-B score, which is based on platelet levels, age and sex, has been shown to accurately predict HCC risk in CHB patients on antiviral treatment in various populations. AIM: We aimed to evaluate the PAGE-B score in predicting HCC risk in Turkish CHB patients on antiviral treatment. METHODS: In this study, we recruited 742 CHB patients who had been treated with tenofovir disoproxil fumarate or entecavir for ≥ 1 year. Risk groups were determined according to the PAGE-B scores as follows: ≤ 9, low; 10-17, moderate and ≥ 18, high. The cumulative HCC incidences in each risk group were computed using Kaplan-Meier analysis and were compared using the log-rank test. The accuracy of the PAGE-B score in predicting HCC risk was evaluated using a time-dependent area under the receiver operating characteristic (AUROC) curve at all study time points. Univariate and multivariate logistic regression analyses were used to assess the risk factors for HCC development. RESULTS: The mean follow-up time was 54.7 ± 1.2 mo. HCC was diagnosed in 26 patients (3.5%). The cumulative HCC incidences at 1, 3, 5 and 10 years were 0%, 0%, 0% and 0.4% in the PAGE-B low-risk group; 0%, 1.2%, 1.5% and 2.1% in the PAGE-B moderate-risk group; and 5%, 11.7%, 12.5%, and 15% in the PAGE-B high-risk group, respectively (log-rank P < 0.001). The AUROCs of the PAGE-B score in the prediction of HCC development at 1, 3, 5 and 10 years were 0.977, 0.903, 0.903 and 0.865, respectively. In the multivariable analysis, older age, male sex, lower platelet levels, presence of cirrhosis, and absence of alanine aminotransferase normalization at month 6 were associated with HCC development (all P < 0.05). CONCLUSION: The PAGE-B score is a practical tool to predict HCC risk in Turkish patients with CHB and may be helpful to improve surveillance strategies.

Effects of Long-Term Tenofovir and Entecavir Treatment on Bone Mineral Density in Patients with Chronic Hepatitis B.

Background: We aimed to investigate the long-term effects of tenofovir disoproxil fumarate and entecavir treatment on bone mineral density and evaluated the fracture risk assessment tool score in patients with chronic hepatitis B. Methods: A total of 58 chronic hepatitis B patients treated with tenofovir disoproxil fumarate (n = 40) and entecavir (n = 18) were included in this prospective study from 2012 to 2016. To evaluate bone mineral density, dual-X-ray absorptiometry, fracture risk assessment tool, and laboratory examinations were performed in all patients first at baseline and second at the end of the study. Results: Age, sex, body mass index, fibrosis score, and viral load were similar in both groups. The mean follow-up was 33 months in the tenofovir disoproxil fumarate group and 31 months in the entecavir group. In patients treated with entecavir, there was no statistically significant difference between baseline and second bone mineral density including lumbar spine (L) and total hip T score. In patients treated with tenofovir disoproxil fumarate, there was a significant difference in the second bone mineral density compared with baseline bone mineral density for L3 (P = .033) and the major fracture risk assessment tool score (P = .03). When patients were divided into 3 groups (normal bone mineral density, osteopenic, and osteoporotic), there was a significant increase in the number of osteopenic patients in the total hip T score after tenofovir disoproxil fumarate treatment (P = .034). Conclusion: Our results suggest a decrease in the bone mineral density for lumbar spine (L3), an increase in the number of patients with hip osteopenia, and major fracture risk assessment tool score after long-term tenofovir disoproxil fumarate treatment in patients with rechronic hepatitis B.

A novel therapeutic approach to NASH: Both polyethylene glycol 3350 and lactulose reduce hepatic inflammation in C57BL/6J mice.

BACKGROUND: The gut-liver axis is one of the most emphasized topics in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Intestinal microbiota dysbiosis has been shown to be a predictor of disease severity and progression to fatty liver disease. Therefore, research addressing gut-based therapies has become popular. OBJECTIVES: To investigate the effect of lactulose and polyethylene glycol 3350 (PEG 3350) in mice with induced obesity and NAFLD at a non-diarrheal dose. MATERIAL AND METHODS: Thirty-six C57BL/6J male mice were divided into 6 groups. The first 2 groups (n = 6 each) were used as an induced obesity model (group A) and NAFLD model (group B) for 8 weeks. The remaining 24 animals were categorized into control diet group, high-fat diet (HFD) group, HFD + lactulose group, and HFD + PEG 3350 group. Serum and liver tissue samples were obtained for biochemical and histopathological analyses, respectively. RESULTS: The HFD + lactulose treatment group displayed a significant decrease in liver weight (1.3 (1.3-1.4) kg compared to 1.8 (1.6-1.9) kg) and NAFLD activity score (NAS) (1.5 (1.0-3.0) compared to 5.0 (4.0-5.0), respectively; p = 0.0043, p = 0.0021) when compared with the HFD group. However, a decrease in body weight (35.0 (34.6-36.0) kg compared to 40.9 (34.7-41.9) kg) and hepatosteatosis (HS) rate (33.3% compared to 100.0%) were not statistically significant (p = 0.1796, p = 0.0606, respectively). The HFD + PEG 3350 treatment group showed a statistically significant decrease in body weight (32.4 (30.2-33.9) kg compared to 40.9 (34.7-41.9) kg), liver weight (1.5 (1.3-1.5) kg compared to 1.8 (1.6-1.9) kg), HS rate (16.7% compared to 100.0%) and NAS (0.5 (0.0-1.0) compared to 5.0 (4.0-5.0); p = 0.0086, p = 0.0086, p = 0.0151, and p = 0.0021, respectively) when compared with the HFD group. CONCLUSIONS: We demonstrated that non-diarrheal dose of lactulose and PEG 3350 reduced hepatic inflammation in mice with induced NAFLD. It was also observed that PEG 3350 decreased HS and body weight. We believe these mechanisms can be utilized as novel therapeutic approaches in NAFLD in prospective human studies.

Polypoid lesions detected in the upper gastrointestinal endoscopy: A retrospective analysis in 19560 patients, a single-center study of a 5-year experience in Turkey.

OBJECTIVE: In our study, we aimed to evaluate the endoscopic features such as prevalence and localization of polypoid lesions determined by us using esophagogastroduodenoscopy and histopathological characteristics of biopsy specimens taken in detail. METHODS: The data of 19,560 patients undergoing upper gastrointestinal endoscopy for any reason between 2009 and 2015 in our endoscopy unit were screened retrospectively and endoscopic and histopathological findings were analyzed in detail. RESULTS: In our study, the polypoid lesion was detected in 1.60% (n=313) of 19,560 patients. The most common localization of the polypoid lesions was determined to be gastric localization (n=301, 96.2%) and antrum with a rate of 33.5% (n=105). When 272 patients in whom biopsy specimen could be taken was investigated, the most frequently seen lesion was polyp (n=115, 43.4%). Hyperplastic polyps (n=81, 29.8%) were the most frequently seen type among all polyps. In histopathological evaluation of the lesions, the prevalence rates of intestinal metaplasia (IM), surrounding tissue IM, atrophy, dysplasia, and neoplasia (adenocarcinoma, squamous cell carcinoma, gastrointestinal stromal tumor, neuroendocrine tumor, and metastatic tumor) among premalignant lesions were determined to be 16.9%, 11.2%, 4.1%, 1.1%, and 3.7%, respectively. CONCLUSION: Polypoid lesions can be seen in endoscopic investigations. In histopathological investigations, while the vast majority of these lesions are benign polyps, some of them are diagnosed as premalignant or malignant lesions. In our study, we determined malignant lesions higher than the similar studies in the literature. This condition shows how effective endoscopic procedure and histopathological evaluation are of vital importance.

Risk of hepatitis B reactivation during anti-TNF therapy; evaluation of patients with past hepatitis B infection.

BACKGROUND/AIMS: Hepatitis B reactivation (HBVR) is an important risk of treatment with tumor necrosis factor inhibitors (anti-TNF). While antiviral prophylaxis is recommended before treatment in HBsAg-positive patients, there is no clear approach for the follow-up or prophylactic treatment of patients with past hepatitis B virus (HBV) infection. The aim of this study was to evaluate patients with past HBV infection treated with anti-TNF for HBVR and/or HBVR-associated biochemical breakthrough. MATERIAL AND METHODS: Patients who received anti-TNF therapy and had past HBV infection (HBsAg negative, anti-HBc IgG positive, anti-HBs negative or positive) were screened and evaluated at 3-month intervals for viral and biochemical breakthrough according to a liver function test (ALT) and HBV DNA level. RESULTS: A total of 653 patients who received anti-TNF therapy were screened. Ninety of these patients had past HBV infection and had not received antiviral prophylaxis. Anti-HBs positivity and isolated anti-HBc IgG positivity were seen in 87.7% (n: 79) and 12.2% (n: 11) of these patients, respectively. No HBVR was seen in 20% (n: 18) of patients who were followed up regularly, and no HBVR-associated biochemical breakthrough was found in patients who were not followed up regularly in terms of HBV DNA level (80%, n: 72) during the follow-up period (26±16 months). CONCLUSION: The use of anti-TNF in patients with past HBV infection has a low risk for HBVR. A follow-up for the ALT and HBV DNA levels at 3-month intervals may be more reasonable than administering antiviral prophylaxis to all patients.

High frequency of gastric cancer precursor lesions in patients with gastric xanthelasma: a prospective case-control study.

OBJECTIVE: An association of gastric cancer and precursor lesions with gastric xanthelasma has frequently been reported. However, the incidence of both gastric xanthelasma and gastric cancer precursor lesions increases with age. The aim of this study was to evaluate the frequency and characteristics of atrophic gastritis, intestinal metaplasia and dysplasia in patients with gastric xanthelasma compared to controls. MATERIAL AND METHODS: Cases with gastric xanthelasma endoscopically and histopathologically were included in this prospective study. The patients included in the study were compared with age- and sex-matched controls in terms of the frequency and characteristics of atrophic gastritis, intestinal metaplasia, dysplasia and cancer. RESULTS: In a series of 1892 upper endoscopies, 108 patients (5.7%) were found to have gastric xanthelasma. The average age of the patients was 61.41 ± 11.43 years. Among the patients, 58 (53.7%) were male. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the xanthelasma group (n = 108) were 31.5, 68.5, 3.7 and 2.8%, respectively. The frequencies of atrophic gastritis, intestinal metaplasia, dysplasia and gastric cancer in the control group (n = 183) were 11.5, 31.7, 0.5 and 0.5%, respectively. Compared to the control group, the frequency of these cancer precursor lesions and the prevalence of advanced stage based on operative link on gastritis intestinal metaplasia assessment were found to be higher in the xanthelasma group (P < 0.05). CONCLUSION: Gastric xanthelasma is associated with an increased frequency of gastric precancerous lesions and should be considered an important marker.

A practical marker to determining acute severe ulcerative colitis: CRP/albumin ratio.

OBJECTIVE: There are many instruments to measure disease activity in ulcerative colitis. While determining clinical activity according to these instruments, many clinical and laboratory parameters are needed to be followed. Determination of disease activity with non-invasive and objective inflammatory indicators may be a practical and objective way. CRP/Albumin ratio (CAR) is an inflammatory marker that is considered to have prognostic value in various cancers, sepsis and acute pancreatitis. In this study, we aim to investigate diagnostic performance CAR in determining the clinical severity of ulcerative colitis. METHODS: Between November 2011 and February 2017, hospital records and follow-up cards of patients with ulcerative colitis were reviewed retrospectively. One hundred forty-nine patients were included in this study. Patient's demographic data, laboratory values, clinical disease activity, according to Truelove & Witts criteria and endoscopic activity according to the Mayo sub-score and treatments, were recorded. Diagnostic performance of CAR analyzed to determine the clinical severity. RESULTS: Of the patients included in this study, 99 (62%) were male, and 50 (38%) were female. Mean age was 45.22±14 years. When patients were grouped into remission, mild, moderate and severe disease according to disease activity, there was a statistically significant difference between CRP, CAR, erythrocyte sedimentation rate (ESR) and albumin levels (p=0.001; p<0.05). Area under the curve (AUC) values for the diagnosis of severe disease were 0.941, 0.931, 0.888 and 0.883 for CAR, CRP, ESR and albumin levels, respectively. Cut-off value to determine severe disease for CAR was 0.6 (sensitivity: 88.9%, specificity of 90.3%, positive predictive value (PPV) 85.1%, negative predictive value (NPV) 92.8%, AUC: 0.941, p<0.001). CONCLUSION: There was a significant relationship between CAR, CRP, ESR and albumin levels and clinical disease severity in patients with ulcerative colitis. CAR is a cheap and practical marker for the diagnosis of acute severe ulcerative colitis.

Echocardiographic epicardial fat thickness measurement: A new screening test for subclinic atherosclerosis in patients with inflammatory bowel diseases.

OBJECTIVE: Inflammatory bowel diseases (IBD) consist of a number of chronic inflammatory diseases. Inflammatory process is known to be involved in all stages of atherosclerosis. Early atherosclerosis is reflected by increased levels of carotid artery intima media thickness (c-IMT) and high-sensitivity C-reactive protein (hs-CRP). Epicardial fat thickness (EFT) strongly influences both the formation and progression of atherosclerosis. Recent studies have demonstrated a relationship between c-IMT and hs-CRP levels and the risk of atherosclerosis in patients with IBD. However, no study has yet compared EFT between patients with IBD and the general healthy population. Hence, this study was designed to further evaluate whether patients with IBD have higher EFT values with increased c-IMT and hs-CRP levels compared to those in the healthy population. METHODS: A total of 110 patients with IBD and 105 healthy volunteers were enrolled into this study. EFT was evaluated by transthoracic echocardiography. c-IMT levels were measured using an ultrasound scanner with a linear probe. The plasma levels of hs-CRP were measured using a highly sensitive sandwich ELISA technique. RESULTS: The hs-CRP and c-IMT levels of patients with IBD were significantly higher than those of the control group. The EFT values of patients with IBD were significantly higher than those of the control group (0.54±0.13 vs. 0.49±0.09, p=0.002). CONCLUSION: Echocardiographic EFT measurements of patients with IBD were significantly higher than those of the normal population, which may be associated with an increased subclinical atherosclerosis risk in these patients.

Therapeutic success with bismuth-containing sequential and quadruple regimens in Helicobacter pylori eradication.

BACKGROUND AND STUDY AIMS: The success rate of Helicobacter pylori (H. pylori) eradication with the classical triple therapy is gradually declining. In this study, we aimed to compare and assess the efficacies of six different eradication regimens including sequential protocols. PATIENTS AND METHODS: Endoscopically confirmed nonulcer dyspepsia patients were enrolled. H. pylori presence was determined either histologically or by a rapid urease test. Treatment-naive patients were randomly assigned to an either one of three 10-day (OAC, OTMB, and OACB) or one of three sequential protocols (OA+OCM, OA+OCMB, and OA+OMDB) (O=omeprazole, A=amoxicillin, C=clarithromycin, T=tetracycline, M=metronidazole, B=bismuth, D=doxycycline). The eradication was assessed 6-8weeks after the completion of the treatment by a 14C-urea breath test. RESULTS: In total, 301 patients were included. Fifty-two percent of the participants (n=157) were female, and the mean age was 44.9years (range=18-70). The intention to treat (ITT) and per protocol (PP) eradication rate for each regimen is as follows: OAC (ITT=61.2%, PP=75%), OTMB (83.3%, 87%), OACB (76.5%, 79.6%), OA+OCM (72.3%, 73.9%), OA+OCMB (82.7%, 89.6%), and OA+OMDB (59.3%, 65.3%). Smoking significantly affected the eradication rate (P=0.04). CONCLUSION: In this study, OTMB and OA+OCMB were significantly superior to the triple therapy and succeeded to reach the eradication rate proposed by the Maastricht consensus (over 80%). These two bismuth-containing regimens could be considered for first-line therapy in the regions with high clarithromycin resistance.

HLA DPB1 15:01 Allele Predicts Spontaneus Hepatitis B Surface Antigen Seroconversion.

AIM: Chronic hepatitis B (CHB) is a global health problem. Recent genome-wide association studies (GWAS) exposed signifi-cant association between the human leukocyte antigen (HLA) class II region, including both DP and DQ loci, and chronic hepatitis B. Previous research also indicated the involvement of adaptive immune system in Hepatitis B seroconversion. The aim of this study is to investigate possible polymorphisms in the HLA-DP locus that can contribute to immune response to Hepatitis B virus (HBV). METHODS: We enrolled 94 chronic hepatitis B (CHB) patients and a control group of 85 spontaneous seroconverted healthy subjects and genotyped HLA-DPB1 alleles by polymerase chain reaction followed by restriction length polymorphism (PCR-RFLP) and Sanger sequencing. RESULTS: Among the 19 DPB1 alleles analyzed in this study, DPB1*15:01 allele was more frequent in the spontaneous sero-converted control group compared to CHB patients (15.3% vs. 1.1%, χ2 = 12.5, OR = 0.06, 95% CI = 0.08-0.046 P < 0.001, Pcorrected < 0.001). DPB1*02:01 and DPB1*10:01 were the other alleles observed more frequently in the control group (38.8% vs. 22.3% P = 0.02 and 16.5% vs. 5.3% P = 0.02, respectively). However associations of these two alleles were lost their significance after Bonferoni's correction (Pcorrected = 0.4 for all). CONCLUSIONS: In conclusion, this study demonstrates that HLA alleles may participate in spontaneous HBsAg seroconversion which is the ultimate target in CHB in Turkish CHB patients.

Is activation in inflammatory bowel diseases associated with further impairment of coronary microcirculation?

BACKGROUND: Inflammatory bowel disease [IBD] includes a number of chronic relapsing diseases. In IBD intestinal microvascular endothelial cells are damaged by an abnormal immune response. Several studies have shown that IBD may cause increment in risk of developing atherosclerosis. IBD in activation was related to enhanced risks of worse cardiovascular [CV] outcome, on the other hand no risk increment was seen in remission comparing to control group in those studies. Coronary Flow Reserve [CFR] reflects coronary microvascular circulation. Coronary microvascular dysfunction may be defined as a predictor of CV outcome combined with previous described atherosclerotic risk factors. The present study was purposed to further evaluate whether or not CFR in the left anterior descending artery [LAD] is disturbed in IBD patients with activation in comparison to remission and healthy subjects. METHODS: 62 patients with IBD and 39 healthy volunteers were enrolled into the study. Patients' demographics were recorded. CFR evaluation of patients with IBD in both activation and remission period and control group were performed with transthoracic echocardiography. RESULTS: CFR was significantly lowest in the active period of the IBD [2.26 [2.08-2.55] vs. 2.55 [2.18-3.00] and 3.10 [2.85-3.29] p<0.001]. CFR is negatively correlated with disease activity scores of IBD. CONCLUSION: This study showed that CFR is more prominently disturbed in patients with IBD in activation. The activation of disease may have a major role in the progression of coronary microcirculatory dysfunction and future cardiovascular events.

Relationship between size of varices and platelet count/spleen size ratio in cirrhotic patients.

OBJECTIVE: This study investigated the relationship between size of gastroesophageal varices and platelet count/spleen diameter ratio in cirrhotic patients. METHODS: The present study included 186 cirrhotic patients in whom gastroesophageal varices were seen during upper gastrointestinal system endoscopy. Clinical features, laboratory parameters, upper gastrointestinal system endoscopy, and abdominal ultrasonographic findings of patients were evaluated retrospectively. Platelet count/spleen diameter ratio (P/S) was calculated by dividing number of platelets in complete blood count (CBC) to largest diameter of spleen. Varices were classified as small, medium, or large, and patients were separated into two groups for comparison: those with small varices and those with medium or large varices. Of the total, 66.7 % of the patients were men (n=124) and 33.3% were women (n=62). Esophageal varices were found in 82.7% and gastric varices were found in 17.3%. RESULTS: Patients with large esophageal varices were found to have significantly lower P/S compared to patients with small esophageal varices (p=0.04). In receiver operating characteristic (ROC) curve analysis, P/S and large varices correlated with 82% sensitivity and 79% positive predictive value. However, no statistically significant correlation between size of varices and P/S was found in patients with gastric varices (p=0.78). CONCLUSION: In patients with esophageal varices, P/S was found to be correlated with large varices with 82% sensitivity. However, this ratio did not predict large varices in patients with gastric varices. Prospective and randomized clinical researches are needed to clarify our findings.

Proteomic profiling of HBV infected liver biopsies with different fibrotic stages.

BACKGROUND: Hepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma. This study aims to enlighten pathways associated with HBV related liver fibrosis for delineation of potential new therapeutic targets and biomarkers. METHODS: Tissue samples from 47 HBV infected patients with different fibrotic stages (F1 to F6) were enrolled for 2D-DIGE proteomic screening. Differentially expressed proteins were identified by mass spectrometry and verified by western blotting. Functional proteomic associations were analyzed by EnrichNet application. RESULTS: Fibrotic stage variations were observed for apolipoprotein A1 (APOA1), pyruvate kinase PKM (KPYM), glyceraldehyde 3-phospahate dehydrogenase (GAPDH), glutamate dehydrogenase (DHE3), aldehyde dehydrogenase (ALDH2), alcohol dehydrogenase (ALDH1A1), transferrin (TRFE), peroxiredoxin 3 (PRDX3), phenazine biosynthesis-like domain-containing protein (PBLD), immuglobulin kappa chain C region (IGKC), annexin A4 (ANXA4), keratin 5 (KRT5). Enrichment analysis with Reactome and Kegg databases highlighted the possible involvement of platelet release, glycolysis and HDL mediated lipid transport pathways. Moreover, string analysis revealed that HIF-1α (Hypoxia-inducible factor 1-alpha), one of the interacting partners of HBx (Hepatitis B X protein), may play a role in the altered glycolytic response and oxidative stress observed in liver fibrosis. CONCLUSIONS: To our knowledge, this is the first protomic research that studies HBV infected fibrotic human liver tissues to investigate alterations in protein levels and affected pathways among different fibrotic stages. Observed changes in the glycolytic pathway caused by HBx presence and therefore its interactions with HIF-1α can be a target pathway for novel therapeutic purposes.

Effect of HLA-DPA1 alleles on chronic hepatitis B prognosis and treatment response.

OBJECTIVE: Chronic hepatitis B (CHB) is a major health problem. The outcome of hepatitis B virus (HBV) infection is associated with variations in HLA-DPA1 alleles. The aim of this study was to investigate possible associations of HLA-DPA1 alleles with treatment response and with hepatitis B virus e antigen (HBeAg) seroconversion. METHODS: Eight different HLA-DPA1 alleles from 246 CHB patients were genotyped by polymerase chain reaction with sequence-specific primers at high resolution to investigate the association of HLA-DPA1 alleles with treatment response, development of cirrhosis, HBeAg seroconversion, and disease reoccurrence upon HBeAg loss. RESULTS: There was no significant association between HLA-DPA1 alleles and treatment response, development of cirrhosis, or HBeAg seroconversion. However, HLA-DPA1*04:01 allele was significantly more frequently found in patients who redeveloped disease upon HBeAg seroconversion (100% vs 36.8%: p=0.037; Fisher's exact test). CONCLUSION: HLA-DPA1*04:01 allele may be a risk factor for reoccurrence of CHB after HBeAg seroconversion.