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Background: Endoscopic mucosal resection (EMR) is the primary treatment modality for superficial gastrointestinal mucosal lesions > 2 cm. However, the procedure carries some risk of complications including bleeding, perforation, and local recurrence. This study aimed to examine factors associated with EMR outcomes, especially in terms of local recurrence., Methods: This study retrospectively evaluated patients who underwent EMR and full closure with prophylactic clips for upper and lower gastrointestinal lesions > 2 cm at Cleveland Clinic Florida, between January 2013 and December 2018 with follow-up endoscopic evaluation for recurrence., Results: A total of 2031 endoscopic polypectomy cases were examined; 307 EMR procedures among 271 patients (52% were female, mean age 65.6 ± 11.1 years) who satisfied the inclusion criteria were included in the study. There were no perforations reported. The rate of post-polypectomy delayed bleeding was 1.6%, and the local recurrence rate in this cohort was 7.1%. Recurrent cases were successfully endoscopically managed. In the multivariate regression analysis, age > 70 years (OR = 3.20, 95% CI 1.17-8.76, p = .023), body mass index (OR = 1.12, 95% CI 1.03-1.23 p = .008), and lesion size ≥ 35 mm (OR = 11.51, 95% CI 3.54-37.40, p =  < .001) were independent predictors for recurrence., Conclusions: Age > 70 years, increased lesion size, and obesity were found to be independent predictors of local recurrence among EMR procedures for gastrointestinal lesions > 2 cm. However, there is a need for larger-scale studies on this topic., (© 2022. Springer Nature Switzerland AG.)

Background: Endoscopic mucosal resection (EMR) involves forming a fluid cushion in the submucosal area with a lifting agent, followed by superficial resection. Orise™ gel is one of the commonly used lifting agents for EMR. We present a case series and literature review that analyzes the characteristic histopathological findings and clinical implications observed where Orise™ gel was used before EMR., Methods: Colon resection specimens and prior EMR specimens where Orise™ gel was used were reviewed for patients undergoing EMR between January 2018 and December 2020. The literature review included relevant studies from the Medline and Cochrane databases from January 2018 to December 2020., Results: A total of 12 colon polyp EMRs using Orise gel were performed during the study period. Seven patients (58.34%) underwent surgical resection. Histological examination revealed that, after the EMR procedure, the Orise™ gel material changed its morphological characteristics over time from a basophilic (bluish) non-inflamed pattern to an eosinophilic (pink) type pattern, eliciting a foreign body reaction. The endoscopic appearance and examination of the excised specimens weeks after injection gave the impression of a mass in some cases. The material was also present transmurally and in some cases in the peri-intestinal adipose tissue., Conclusions: It was observed that Orise™ gel use elicits a foreign body-type granulomatous reaction. This potential side effect may lead to overdiagnosis of a mass/lesion and unnecessary surgical interventions. This case series and review of the literature aims to increase awareness of the changes caused by Orise™ gel in the gastrointestinal tract., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and its incidence is increasing. Nonalcoholic steatohepatitis (NASH), the progressive form of the disease, can lead to end-stage liver disease. The pathogenesis of the disease is not fully understood, and there is currently no specific treatment. Therefore, an effective and reliable treatment modality is needed. In recent years, the inflammasome has been shown to play a vital role in many stages of NAFLD pathogenesis. In particular, the detection, by toll-like receptors, of pathogen-associated molecular patterns induced by the gut-liver axis triggers the formation of the NLRP3 (NLR family pyrin domain-containing protein 3) inflammasome. Stimulation of damage-associated molecular patterns also activates the NLRP3 inflammasome. The activated inflammasome has caspase-1 activity, which leads to the release of interleukin (IL)-1 and IL-18 and formation of pores in the cell wall. This process spreads the inflammatory process to the outside of the cell and induces inflammatory cell death (pyroptosis). Subsequent progression of the inflammatory process leads to fibrosis. Recent evidence suggests that the NLRP3 inflammasome may be a potential target for the treatment of NASH. The discovery of specific NLRP3 inflammasome blockers in recent years and evidence of their positive effects in experimental models support this therapeutic approach. In this article, we discuss recent evidence on the pathogenesis of NAFLD, the role of the inflammasome in the pathogenesis of NAFLD, and the potential effects of inhibition of the inflammasome., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Aim: There is limited data regarding the safety of endoscopic mucosal resection (EMR) in the cirrhotic population. Our study aimed to evaluate the safety of colonoscopic EMR in cirrhosis., Materials and Methods: This was a retrospective review of cirrhotics who underwent colonic EMR at 8 Cleveland Clinic Centers between January 1, 2006, and December 31, 2018. Patient data including polyp details and complications occurring within 30 days of the procedure were noted. Univariable and multivariable logistic regression analyses were conducted to find risk factors for post-EMR bleeding., Results: A total of 238 patients who underwent EMR were included. There were 145 males (60.9%) and the mean age was 61.9±8.6 years. Immediate and delayed bleeding, and postpolypectomy syndrome rates were 9.2%, 5.8%, and 1.3%, respectively. Significant risk factors for postpolypectomy bleeding were: increased age (P=0.001), procedure duration >37 minutes (P=0.001), antiplatelet use within 5 days (P=0.023), and lesion diameter >15 mm (P=0.004). Multivariable analysis revealed independent predictors of procedure-related bleeding: age above 65 years [odds ratio (OR) 2.14, P=0.044], antiplatelet use within 5 days (OR 2.42, P=0.047), right colon polyp (OR 3.51, P=0.001), and lesion diameter >15 mm (OR 3.22, P=0.003)., Conclusions: EMR in cirrhotics has an acceptable bleeding risk. Age above 65 years, right colon polyp, polyp size >15 mm, and use of antiplatelets within 5 days are independent risk factors for bleeding., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Our study aimed to examine the relationship of the visceral adiposity index (VAI) with clinical and histological parameters in biopsy-proven nonalcoholic fatty liver disease (NAFLD) cases and evaluate its place in clinical practice. Materials and Methods: The study included 57 biopsy-proven NAFLD cases and 57 healthy controls. The VAI values of the cases were calculated with the formula based on body mass index, waist circumference, triglycerides, and high-density lipoprotein cholesterol levels. The relationships between VAI values and clinical and histological parameters were examined. Results: While the VAI was significantly higher in the NAFLD cases in comparison to the control group (3.5 ± 3.09 vs. 1.60 ± 0.98, respectively, P  < 0.001), this difference was more noticeable in the nonalcoholic steatohepatitis (NASH) group (3.60 ± 3.35) ( P  < 0.001). In distinguishing the NAFLD group and the healthy group in VAI, it was determined that VAI had a sensitivity of 72%, specificity of 68%, and an area under the receiver operating characteristic curve value of 76.9%. No significant relationship was found between the histological parameters and VAI scores. Conclusions: Our study showed that VAI was increased in the NAFLD cases. This increase was observed to be more noticeable in especially the NASH cases. It is possible for this index to be a practical modality that could be used in clinical practice in prediction of especially NASH cases, which constitute the progressive form of the disease, but in this sense, there is a need for further studies.

Background: Liver transplantation (LT) for hepatocellular carcinoma (HCC) is curative in most cases; however, recurrence is observed in some patients. The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score is an externally validated scoring system for prediction of post-LT HCC recurrence. The Cleveland Clinic Florida Scoring System (CCFSS) is a potential new scoring system for prediction of HCC recurrence. Our study aimed to compare the RETREAT and CCFSS., Methods: We conducted a retrospective cohort study of 52 adult patients with HCC who underwent LT at a tertiary care center. Mantel-Haenszel chi-square analyses were conducted to compare the RETREAT and CCFSS classifications for detecting HCC recurrence., Results: A total of 52 patients underwent LT. The median follow-up period was 37 months. Four patients had post-LT HCC recurrence, with all recurrences occurring within 2 years of LT. The RETREAT score was better able to detect low, moderate, and high levels of risk (P < .001), compared to the CCFSS score (P = 0.480). Both risk scores had a sensitivity of 75%; the specificity of the RETREAT score was 95.8%, whereas the specificity of the CCFSS was 60.4%. Alpha-fetoprotein level at the time of LT was associated with HCC recurrence (P = .014)., Conclusions: This is the first study to evaluate the CCFSS as a potential new scoring system to predict HCC recurrence after LT. The RETREAT score is more specific than the CCFSS. The incorporation of alpha-fetoprotein level at the time of LT improves the estimation of HCC recurrence in the post-LT period., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective and study aims  Patients with left-ventricular assist devices (LVADs) have an increased risk of gastrointestinal bleeding, especially from the small bowel, often necessitating evaluation with balloon-assisted enteroscopy (BAE). Our study aimed to assess the periprocedural safety and utility of BAE for gastrointestinal bleeding in patients with LVADs. Patients and methods  This was a multicenter retrospective cohort study of adults with LVADs who underwent BAE between January 2007 to December 2018. Results  Thirty-four patients underwent a total of 46 BAEs (9 were single-balloon enteroscopies [SBEs] and 37 were double-balloon enteroscopies [DBEs]). Mean age of patients was 66.4 ± 8.3 years. Patients tolerated anesthesia well, without complications. There were no complications from the BAE itself. One patient required repeat BAE due to a progressive drop in hemoglobin and another patient developed paroxysmal supraventricular tachycardia. One patient died within 72 hours of the procedure due to worsening of LVAD thrombosis. Diagnostic yields were 69.6 % for all procedures, 73.0 % for DBE and 55.6 % for SBE ( P  = 0.309). Therapeutic yields were 67.4 % overall: 73.0 % for DBE and 44.4 % for SBE ( P  = 0.102). In those that presented with overt gastrointestinal bleeding, DBE had a higher diagnostic yield compared to SBE (84.2 % vs. 42.9 %; P  = 0.057) and a significantly higher therapeutic yield (84.2 % vs. 28.6 %; p = 0.014). Conclusions  This is the largest multicenter study of patients with LVADs who underwent DBE. BAE appears to be a safe and useful modality for the evaluation of gastrointestinal bleeding in these patients., Competing Interests: Competing interests The authors declare that they have no conflict of interest.

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 14 C-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., (Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide. Along with the increase in the incidence of NAFLD and associated obesity, an increase in gallbladder disease (GD) has been noted. This has led to the identification of a new disease entity called fatty GD. There is a gap in the literature on the dynamics of gallbladder function in patients with NAFLD., Methods: An observational case-control study, a total of 50 patients with biopsy proven NAFLD without gallbladder stone/sludge and 38 healthy comparison subjects were enrolled. Fasting, postprandial gallbladder volumes (PGV), gallbladder ejection fraction (GEF), and fasting gallbladder wall thickness (FGWT) were measured by real-time 2-dimensional ultrasonography., Results: Fasting gallbladder wall thickness, fasting gallbladder volumes and PGV were significantly higher in patients with NAFLD than control subjects (P < 0.001, P = 0.006, and P < 0.001, respectively). Gallbladder ejection fraction was significantly lower in the NAFLD group than the controls (P = 0.008). The presence of NAFLD was an independent predictor for GEF, PGV, and FGWT. Also, steatosis grade was an independent predictor for GEF, and GEF was significantly lower in the nonalcoholic steatohepatitis (NASH) subgroup than the controls., Conclusions: Gallbladder dysfunction and increase in gallbladder wall thickness exists in asymptomatic (without stone/sludge and related symptoms) patients with NAFLD and are useful in identifying fatty GD. Measurement of these variables in NAFLD patients may be useful in identifying those at higher risk for GD.

Aim: To analyze the relationship between the serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) levels and clinical and histopathological features of biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) patients., Methods: Fifty-three consecutive, biopsy-proven NAFLD patients (31 males and 22 females, mean age 42.5 ± 9.6 years) and 26 age- and gender-matched, healthy controls (14 males and 12 females, mean age 39 ± 10.7 years) were included. The patients with NAFLD were consecutive patients who had been admitted to the hepatology outpatient clinic within the last year and had been diagnosed with NAFLD as the result of liver biopsy. The healthy controls were individuals who attended the outpatient clinic for routine health control and had no known chronic illnesses. The histological evaluation was conducted according to the NAFLD activity scoring system recommended by The National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. The serum LOX-1 levels were measured using an ELISA kit (Life Science Inc. USCN. Wuhan, Catalog No. E1859Hu) in both patients and healthy controls. A receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of LOX-1 and thereby distinguish between patients with nonalcoholic steatohepatitis (NASH) and healthy controls. A P-value < 0.05 was considered statistically significant., Results: NAFLD and healthy control groups were similar in terms of age and sex. NAFLD patients consisted of 8 patients with simple steatosis (15%), 27 with borderline NASH (51%) and 18 with definitive NASH (34%). Metabolic syndrome was found in 62.2% of the patients with NAFLD. The mean serum LOX-1 level in biopsy-proven NAFLD patients was 8.49 ± 6.43 ng/mL compared to 4.08 ± 4.32 ng/mL in healthy controls (P = 0.001). The LOX-1 levels were significantly different between controls, simple steatosis and NASH (borderline+definite) cases (4.08 ± 4.32 ng/mL, 6.1 ± 6.16 ng/mL, 8.92 ± 6.45 ng/mL, respectively, P = 0.004). When the cut-off value for the serum LOX-1 level was set at 5.35 ng/mL, and a ROC curve analysis was performed to distinguish between steatohepatitis patients and controls; the sensitivity and specificity of the serum LOX-1 level were 69.8% and 69.2%, respectively., Conclusion: The serum LOX-1 levels were significantly higher in NAFLD patients than in healthy controls. Additionally, the serum LOX-1 levels could differentiate between steatohepatitis patients and healthy controls.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD is a complex disease and inflammation is a crucial component in the disease pathogenesis. Recent genome wide association studies in hepatology area highlighted significant relations with human leukocyte antigen (HLA) DQ region and certain liver diseases. The previous animal models also emphasized the involvement of adaptive immune system in the liver damage pathways. To investigate possible polymorphisms in the HLA region that can contribute to the immune response affecting the NAFLD, we enrolled 93 consecutive biopsy proven NAFLD patients and a control group consisted of 101 healthy people and genotyped HLA DQB1 alleles at high resolution by sequence specific primers-polymerase chain reaction. The mean NAFLD activity score (NAS) was 5.2 ± 1.2, fibrosis score was 0.9 ± 0.9, ALT was 77 ± 47.4 U/L, AST was 49.4 ± 26.3 U/L. Among 13 HLA DQB1 alleles analyzed in this study, DQB1*06:04 was observed significantly at a more frequent rate among the NAFLD patients compared to that of healthy controls (12.9 vs. 2 % χ(2) = 8.6, P = 0.003, P c = 0.039, OR: 7.3 95 % CI 1.6-33.7). In addition, the frequency of DQB1*03:02 was significantly higher in the healthy control group than the NAFLD patients (24.8 vs. 7.5 %, χ(2) = 10.4, P = 0.001, P c = 0.013, OR: 0.2, 95 % CI 0.1-0.6). NAFLD patients were grouped according to their fibrosis score and NAS. The distribution of DQB1 alleles over stratified NAFLD patients did not reveal any statistically significant relation. Taken together, immune repertoire of individuals may have an effect on NAFLD pathogenesis and therefore, in NAFLD, adaptive immunity pathways should be investigated.

Sirtuins (SIRTs) are members of the silent information regulator-2 family and act as nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases. The de-acetylation of proteins and histones results in an up- or down-regulation of gene transcription and protein function. In recent years, the regulatory action of the deacetylation activity of SIRT1 has been shown to have a positive impact on the pathophysiological mechanisms of nonalcoholic fatty liver disease (NAFLD). Among the effects of SIRT1 are: its healing activity on insulin sensitivity, thereby ameliorating glycemic regulation; its mimetic activity on calorie restriction; its antihyperlipidemic activity on lipid homeostasis via the liver, adipose tissues and skeletal muscles; its anti-inflammatory activities; its protective effects against cardiovascular events and endothelial dysfunction; its positive influence on autophagy, apoptosis and cancer; and finally, its anti-aging activity. The current approach for the treatment of NAFLD involves the treatment of etiological factors and recommendation of life-style changes including more physical activity and a low-calorie diet. However, there is no specific medical treatments for NAFLD. The therapeutic potential of SIRT1 activity in the treatment of NAFLD discovered in humans has been presented in this article. In this review, the potential effects of SIRT1 activation on NAFLD-related pathophysiological mechanisms and on the treatment of NAFLD are discussed.

Aim: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B., Methods: Patient records at a single institution's hepatology clinic were reviewed. Demographic data, laboratory results, endoscopy results, virological parameters, biopsy scores and treatment statuses were recorded. In total, 355 patients were eligible for the study, of whom 226 (63.7%) were male. Overall, 82 (23.1%) were hepatitis B early antigen (HBeAg) positive, 87 (24.5%) had cirrhosis, and 66 (18.6%) had inactive disease. The presence of DQB1 and DRB1 alleles was determined by polymerase chain reaction with sequence-specific primers. The distribution of the genotyped alleles among patients with cirrhosis and patients with chronic active hepatitis was analyzed., Results: The most frequent HLA DQB1 allele was DQB1*03:01 (48.2%), and the most frequent HLA DRB1 allele was DRB1*13/14 (51.8%). DQB1*05:01 was more frequent in patients with active disease than in inactive patients (27% vs 9.1%; P = 0.002, Pc = 0.026). DRB1*07 was rare in patients with cirrhosis compared with non-cirrhotics (3.4% vs 16%; P = 0.002, Pc = 0.022). Older age (P < 0.001) and male gender (P = 0.008) were the other factors that affected the presence of cirrhosis. In a multivariate logistic regression analysis, DRB1*07 remained a significant negative predictor of cirrhosis (P = 0.015). A bioinformatics analysis revealed that a polymorphic amino acid sequence in DRB1*07 may alter interaction with the T-cell recognition site., Conclusion: This study demonstrates that HLA alleles may influence cirrhosis development and disease activity in Turkish chronic hepatitis B patients.

Background/aims: We sought to examine whether the presence of gallstone disease (GD) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) is associated with liver fibrosis and histological nonalcoholic steatohepatitis (NASH) score., Methods: We included 441 Turkish patients with biopsy-proven NAFLD. GD was diagnosed in the presence of sonographic evidence of gallstones, echogenic material within the gallbladder with constant shadowing and little or no visualization of the gallbladder or absence of gallbladder at ultrasonography, coupled with a history of cholecystectomy., Results: Fifty-four patients (12.2%) had GD (GD+ subjects). Compared with the GD- subjects, GD+ patients were older, had a higher body mass index and were more likely to be female and have metabolic syndrome. However, GD+ patients did not have a higher risk of advanced fibrosis or definite NASH on histology. After adjustment for potential confounding variables, the prevalence of GD in NAFLD patients was not associated with significant fibrosis (≥2) (odds ratio [OR], 1.06; 95% confidence interval [CI], 0.53 to 2.21; p=0.68) or definite NASH (OR, 1.03; 95% CI, 0.495 to 2.12; p=0.84)., Conclusions: The presence of GD is not independently associated with advanced fibrosis and definite NASH in adult Turkish patients with biopsy-proven NAFLD.

Aims: Growing evidence suggests that not only type 2 diabetes (T2D) but also prediabetes (PD) is common in patients with non-alcoholic fatty liver disease (NAFLD). However, few data exist on how PD impacts the histological characteristics of NAFLD patients. In this exploratory study, we sought to investigate the associations of PD and T2D with the severity of the histological features in patients with NAFLD., Methods: The population consisted of 280 patients with biopsy-proven NAFLD. The associations of PD and T2D with the severity of histological features of NAFLD were analyzed using multiple logistic (or ordinal logistic) regression models after adjustment for confounding factors., Results: PD and T2D was noted in 102 (36.4%) and 92 (32.8%) of patients, respectively. Of the 92 patients with T2D, ten (10.9%) were diagnosed de novo after the OGTT. PD and T2D were significantly associated with more severe portal inflammation (P<0.01); the adjusted odds ratios (ORs) of PD and T2D for having a higher grade of portal inflammation were 1.8 [95% CI, 1.1, 3.2] and 2.6 [95% CI, 1.3, 5.8]), respectively. A similar relationship was observed for liver fibrosis (P<0.001); specifically, the adjusted ORs of PD and T2D for having a higher grade of hepatic fibrosis were 2.4 [95% CI, 1.3, 3.7] and 3.8 [95% CI, 1.9, 6.1]), respectively., Conclusion: Not only T2D but also PD is independently associated with portal inflammation and fibrosis in NAFLD patients. PD may be useful as a clinical indicator of patients who are likely to have already more severe histological findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Recent studies have suggested that bacterial overgrowth and endotoxemia along with its receptor, Toll-like receptor 4 (TLR-4), play a role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The present study was designed to test and evaluate the TLR4 gene polymorphism in patients with NAFLD in comparison to healthy controls., Methods: A total of 119 patients [mean (standard deviation, SD) age 43.4 (11.5) years, 55.5% were males] with NAFLD and 80 healthy controls [mean (SD) age 40.9 (8.1) years, 67.5% were females)] were evaluated in terms of patient demographics, anthropometrics, blood biochemistry, liver histology, and ultrasonographic (USG) findings. Histological evaluation was performed in 111 patients, and blood samples were collected from 119 patients with NAFLD and 80 healthy persons. Allelic variants of TLR4 (Asp299Gly and Thr399Ile) were assayed by real-time PCR. Genomic DNA was amplified using FAM/VIC primers specific for allelic variants of TLR4 Asp299Gly and Thr399Ile with real-time PCR. Amplicons were analyzed with high-resolution melting on a Light Cycler 480 for detecting different melting patterns of polymorphic and wild-type alleles., Results: The number of the subjects with heterozygous mutation at genotype 299 (Asp299Gly) was significantly lower in the NAFLD than in the control group (23.8 vs. 10.9%, P=0.027). Logistic regression analysis revealed that female gender [odds ratio (OR)=2.984, 95% confidence interval (CI) 1.561-5.360, P=0.001] and heterozygous (Asp299Gly) mutation at codon 299 (OR=2.998, 95% CI 1.325-6.783, P=0.008) were the significant predictors of higher likelihood of TRL4 gene polymorphism-related prevention of NAFLD., Conclusions: As the first-time-in-humans controlled study related to investigation of TLR4 gene polymorphism in NAFLD, our findings contribute to the available data that TLR-4 signaling is pivotal for the pathogenesis of NASH and indicate that the TLR4 codon 299 heterozygous gene mutation (Asp299Gly) in humans may have a preventive role against the genesis of NAFLD.

Background: Nonalcoholic fatty liver disease (NAFLD) encompasses a disease spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). We aimed to evaluate left ventricular (LV) systolic function using two-dimensional speckle-tracking echocardiography (2D-STE) in patients with NAFLD and to investigate whether any changes exist among the subgroups of NAFLD., Materials and Methods: We included 55 NAFLD patients and 21 healthy controls. The diagnosis of NAFLD was made on the basis of liver biopsy. After the patients were categorized into groups according to their histopathological analysis (simple steatosis, borderline NASH, and definitive NASH), all patients underwent echocardiography. In the 2D-STE analysis of the LV global longitudinal strain (G-LS), strain rate in systole (G-SRsys), strain rate in early diastole (G-SRearly), and strain rate in late diastole (G-SRlate) values were obtained., Results: G-LS and G-SRsys values were lower in the NAFLD group. Although there was a significant difference in the G-LS between controls and simple steatosis, borderline NASH, and definitive NASH, no significant differences were found between NAFLD groups. To investigate whether impaired LV systolic dysfunction, determined using 2D-STE, is the consequence of NAFLD components, we included a subgroup. A total of 11 patients with NAFLD who were normotensive, nondiabetic, nonobese, and had a normal lipid profile and low homeostasis model assessment of insulin resistance (HOMA-IR) values were included. Echocardiographic abnormalities in systolic function were not different between this subgroup of NAFLD and healthy individuals., Conclusion: Patients with NAFLD and its subgroups have evidence of subclinical myocardial dysfunction in relation to the presence of insulin resistance. 2D-STE could not be used for differentiation of the NAFLD subgroups.

The presence of the metabolic syndrome is a strong predictor for the presence of NASH (non-alcoholic steatohepatitis) in patients with NAFLD (non-alcoholic fatty liver disease). In the present study, we assessed LA (left atrial) deformation parameters in patients with NAFLD using 2D-STE (speckle tracking echocardiography) and to investigate if any changes exist between subgroups of the NAFLD. A total of 55 NAFLD patients and 21 healthy controls were included in the study. The diagnosis of NAFLD was based on liver biopsy. After patients were categorized into groups according to histopathological analysis (simple steatosis, borderline NASH, definitive NASH), all patients underwent echocardiography with Doppler examination. In the 2D-STE analysis of the left atrium, LA-Res (peak LA strain during ventricular systole), LA-Pump (peak LA strain during atrial systole), LA-SR(S) (peak LA strain rate during ventricular systole), LA-SR(E) (peak LA strain rate during early diastole) and LA-SR(A) (peak LA strain rate during atrial systole) were obtained. LA-Res, LA-Pump and LA-SR(A) were lower in the NAFLD group than in the control group. LA-Res was found to be significantly lower in NAFLD subgroups compared with healthy subjects (43.9±14.2 in healthy controls compared with 31.4±8.3 with simple steatosis, 32.8±12.8 with borderline NASH and 33.8±9.0 with definitive NASH). LA-Pump was significantly lower in the NAFLD group (18.2±3.1 in healthy controls compared with 13.3±4.7 with borderline NASH and 14.4±4.7 with definitive NASH). There were significant differences in LA-SR(A) between healthy controls compared with simple steatosis and borderline NASH (-1.56±0.36 compared with 1.14±0.38 and 1.24±0.32 respectively). Correlation analysis showed significant correlation of LA-Res values with E (early diastolic peak velocity)/E(m) (early diastolic mitral annular velocity) ratio (r=-0.50, P≤0.001), with LAVI (LA volume index; r=-0.45, P≤0.001) and with V(p) (propagation velocity; r=0.39, P≤0.001). 2D-STE-based LA deformation parameters are impaired in patients with NAFLD with normal systolic function. Although LA-Res and pump function parameters might be useful in estimating LV (left ventricular) filling pressure in the NAFLD patient group, it could not be used for differentiating the subgroups.

Aim: To investigate serum insulin-like growth factor-binding protein 5 (IGFBP-5) levels and intestinal IGFBP-5 expression in patients with Crohn's disease (CD)., Methods: We analyzed the serum concentrations and intestinal expression of IGFBP-5 in 42 patients with CD, of whom 26 had endoscopically or radiologically proven stricture formation. Nine of the 42 patients had active disease, with a Crohn's disease activity index > 150. Serum IGFBP-5 levels were analyzed in 20 healthy controls matched by sex and age to the CD patients. Serum IGFBP-5 was measured using an enzyme-linked immunosorbent assay. Intestinal tissue was obtained from patients through endoscopic biopsies. IGFBP-5 expression was detected using immunohistochemistry and was scored semiquantitatively., Results: The median serum IGFBP-5 concentrations of CD patients were significantly lower compared with healthy controls [median 7.2 (IQR: 5.5-11.3) ng/mL vs 11.3 (8.0-44.6) ng/mL, P < 0.001]. There was no significant difference between median serum IGFBP-5 levels in CD patients with or without stricture formation [6.9 (5.5-11.3) ng/mL vs 7.8 (5.3-10.1) ng/mL, P = 0.815]. The serum IGFBP-5 levels were not significantly different between patients with active disease and inactive disease [7.2 (6.5-7.6) ng/mL vs 7.2 (5.5-11.3) ng/mL, P = 0.890]. However, a significant correlation was observed between serum IGFBP-5 levels and platelet count (PLT) (r = 0.319, P = 0.0395). No significant correlation was found between tissue IGFBP-5 immunohistochemical staining intensity scores and serum IGFBP-5 levels. No significant difference was found when comparing the serum IGFBP-5 levels among the patients with different tissue IGFBP-5 staining scores (absent/very weak, weak, moderate or strong). There was a significant correlation between tissue IGFBP-5 staining scores and white blood cell count (r = 0.391, P = 0.01) and PLT (r = 0.356, P = 0.021)., Conclusion: Our results indicate that serum IGFBP-5 concentrations were lower in CD patients compared to healthy controls regardless of disease activity or the presence of stricture formation.

Background: Chronic hepatitis B treatment with oral antiviral drugs is a long course. During this course, antiviral resistance is a serious issue, particularly, if genetically low barrier drugs are in use. Host immunity is accepted to have an effect on antiviral resistance development. The earliest clinical sign of drug resistance is virologic breakthrough. In this study, we aimed to investigate the relation between HLA-DQB1 alleles and virologic breakthrough events., Subjects and Methods: The patient records at single institution hepatology clinic were reviewed. Local institution ethics committee approval was taken. The patients' demographic data, virologic parameters, treatment statues were noted. Patients who had received lamivudine or adefovir were recruited and grouped into two according to virologic breakthrough occurrence. Patients who were not compliant to the given treatment were excluded. Blood samples were taken for DNA extraction. HLA-DQB1 alleles were determined at high level by sequence-specific primers-polymerase chain reaction. The distribution of DQB1 alleles among groups was analyzed., Results: One hundred ninety-eight patients were eligible for the study. Ninety-six of them had virologic breakthrough where 102 did not have. DQB1 0503 allele was more frequent in patients without breakthrough (28.4% vs. 12.4%, P=0.006). In univariate analysis, HBeAg seropositivity (P<0.001), absence of cirrhosis (P=0.007), younger age (P=0.002) and higher pretreatment logDNA (P<0.001) were related to breakthrough events. However, in multivariate analysis only logDNA (P<0.001) and DQB1*0503 (P=0.02) allele revealed statistically significant relation with breakthrough events., Conclusion: Host immunity may have an effect on outcome during treatment with oral antiviral drugs. A patient with better immunologic profile may suppress the viral replication better and this may cause less resistance occurrence during treatment with genetically low barrier drugs., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

In this study, we aimed to evaluate the endothelial functions in patients with nonalcoholic fatty liver disease (NAFLD). In this observational case-control study, a total of 51 patients with NAFLD in study group and a total of 21 with age- and sex-equivalent individuals in control group were enrolled. In both patients and control groups, levels of asymmetric dimethylarginine (ADMA), systemic endothelial function (brachial artery flow-mediated dilation) (FMD) and carotid artery intima-media thickness (C-IMT) were measured. FMD and C-IMT were evaluated by vascular ultrasound. Plasma levels of ADMA were measured by ELISA. C-IMT was significantly higher in patients with NAFLD group than control group (0.67 ± 0.09 vs. 0.52 ± 0.11 mm, P < 0.001). The average C-IMT measurements were found in groups of control, simple steatosis, and NAFLD with (borderline and definite) NASH as 0.52 ± 0.11, 0.63 ± 0.07, and 0.68 ± 0.1 mm, respectively. The differences between groups were significant (P < 0.001). Measurement of brachial artery FMD was significantly lower in patients with NAFLD group compared to control group (7.3 ± 4.8 vs. 12.5 ± 7.1 %, P < 0.001). FMD measurements in groups of control, the simple steatosis, and NAFLD with NASH as 12.5 ± 7.1, 9.64 ± 6.63, and 7.03 ± 4.57 %, respectively, and the differences were statistically significant (P < 0.001). The increase in C-IMT and decrease in FMD was independent from metabolic syndrome and it was also more evident in patients with simple steatosis and NASH compared to control group. There was no significant difference between the control and NAFLD groups in terms of plasma ADMA levels (0.61 ± 0.11 vs. 0.69 ± 0.37 μmol/L, P = 0.209). Our data suggested that NAFLD is associated with endothelial dysfunction and increased earlier in patients with atherosclerosis compared to control subjects.

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 (β=0.294, p<0.01) and serum aminotransferase levels (aspartate aminotransferase: β=0.295, p<0.01; alanine aminotransferase; β=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., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aims and Background: Nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are two major causes of liver disease worldwide. Epidemiological and clinical data have clearly demonstrated that NAFLD and its associated metabolic abnormalities are a risk factor for HCC. Traditionally, the mechanisms whereby NAFLD acts as a risk for HCC are believed to include replicative senescence of steatotic hepatocytes and compensatory hyperplasia of progenitor cells as a reaction to chronic hepatic injury. Recent years have witnessed significant advances in our understanding of the mechanisms underlying the link between NAFLD and HCC., Methods: In the present review, we provide an update on the pathophysiological pathways linking NAFLD and its associated metabolic derangements to malignant hepatic transformation, with a special focus on insulin resistance, adipokines, inflammation, and angiogenesis. We will also discuss the potential therapeutic implications that such molecular links carry., Results: Although treating NAFLD could reduce the risk of malignant hepatic transformation, no long-term studies focusing on this issue have been conducted thus far. Insulin resistance, inflammation as well as derangements in adipokines and angiogenic factors associated with NAFLD are closely intertwined with the risk of developing HCC., Conclusions: Traditional therapeutic approaches in NAFLD including metformin and statins may theoretically reduce the risk of HCC by acting on common pathophysiological pathways shared by NAFLD and HCC.

Background. To investigate the relationship between DR-70 serum levels and dysplastic colon polyps. Materials and Methods. A total of 130 patients with adenomatous polyps detected by colonoscopy and divided into two groups including low versus high grade polyp, along with 50 healthy blood donors were included in the study. Blood samples from each participant were analyzed for serum CEA and DR-70 levels. Results. No statistically significant differences were observed between the two groups in terms of age or gender. The median DR-70 level was 0.5  μ g/mL in the healthy control group and 1.1  μ g/mL in group 1b (i.e., the high grade polyp) (P < 0.001). DR-70 was higher in group 1b as compared to group 1a (P < 0.001). However, the median DR-70 values for the low grade polyp group (i.e., group 1a) and the control group were similar (P = 0.067). In order to determine independent predictors of high grade dysplasia, CEA, DR-70, polyp size, and age parameters were subjected to multiple logistical regression analyses via the Enter method; the model was statistically significant (P < 0.001). Conclusions. DR-70, a marker used to measure FDP, which is generated by all major cancers, is a potential marker to identify patients with advanced adenomatous polyps, that is, precursors of colorectal cancer.

Background and Aims: Syndecan-1 (CD138) is a transmembrane heparan sulfate proteoglycan expressed in the liver which may exert metabolic effects by mediating the hepatic clearance of triglyceride-rich lipoproteins. In the present study, we assayed serum levels and the hepatic expression of syndecan-1 and examined their association with clinical, biochemical, and histologic phenotypes in patients with histology-proven nonalcoholic fatty liver disease (NAFLD)., Methods: A total of 59 patients with biopsy-proven NAFLD and 54 matched controls were enrolled. The analysis of syndecan-1 expression in liver biopsies was performed by immunohistochemistry on formalin-fixed, paraffin-embedded samples. Serum syndecan-1 levels were measured by ELISA., Results: NAFLD patients had significantly higher serum syndecan-1 levels [median: 61 ng/mL (interquartile range: 36-97 ng/mL)] than controls [median: 37 ng/mL (interquartile range: 25-59 ng/mL, Mann-Whitney U test, p < 0.001]. However, we did not find any significant association between serum syndecan-1 and the mean syndecan-1 immunohistochemical score (n = 59, r = 0.064, p = 0.63). Interestingly, the syndecan-1 immunohistochemical score was an independent predictor of HDL cholesterol in NAFLD patients (β = 0.27; t = 1.99, p < 0.05)., Conclusions: Our data suggest that serum syndecan-1 levels are raised in patients with NAFLD. Moreover, the syndecan-1 immunohistochemical score in the liver is independently associated with HDL cholesterol in this group of patients. These pilot results support further investigation of this molecule in metabolic liver diseases.

Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in many countries, and its prevalence is increasing. NAFLD is often considered to be a hepatic component of metabolic syndrome, and studies have established that insulin resistance plays a major role in the pathogenesis of NAFLD. Treatments for NAFLD primarily target insulin resistance. Interestingly, the most common environmental cause of insulin resistance is diet. This article examines the correlations between NAFLD and diet and provides some diet recommendations based on the most current data available.

Objective: Currently, nonalcoholic fatty liver disease (NAFLD) itself has been accepted as an atherosclerotic risk factor and related to increased cardiovascular disease risk. In this study, we aimed to investigate the relationship of epicardial fat thickness (EFT), a parameter associated with atherosclerosis in recent years, with carotid artery intima-media thickness (C-IMT), another parameter of subclinical atherosclerosis., Design and Methods: We investigated 57 patients with biopsy-proven NAFLD and 30 age-matched and sex-matched controls. EFT was obtained by transthoracic echocardiography and C-IMT was evaluated by an ultrasonographic measurement using a linear type B-mode probe., Results: EFT and C-IMT were significantly higher in NAFLD patients compared with the controls (EFT: 0.58 ± 0.18 vs. 0.36 ± 0.17 cm, P<0.001 and C-IMT: 0.64 ± 0.1 vs. 0.52 ± 0.1 mm, P<0.001, respectively). We found a statistically significant correlation between EFT and BMI, C-IMT, waist circumference, homeostasis model assessment of insulin resistance, and nonalcoholic steatohepatitis scores in both groups. Stepwise regression analysis showed that C-IMT (β=0.36, t=2.86, P=0.006) and waist circumference (β=0.3, t=2.44, P=0.018), in the order they entered into the model, were independent predictors of EFT in patients with NAFLD., Conclusion: Our findings indicate that EFT and C-IMT were significantly higher in patients with NAFLD compared with the controls and waist circumference and C-IMT are independent predictors for EFT in patients with NAFLD.

Background: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is one of the most common causes of chronic liver disease, worldwide. Lipoprotein-associated phospholipase A2 (Lp-PLA2) was recently characterized as a novel inflammatory biomarker that is correlated with several components constituting the metabolic syndrome., Methods: In this study, we determined the serum levels of Lp-PLA2 in patients with definite nonalcoholic steatohepatitis (NASH, n=25), borderline NASH (n=22), simple fatty liver (n=10), and healthy controls without evidence of liver disease (n=38). The levels of Lp-PLA2 were measured by enzyme-linked immunosorbent assay and compared in the four study groups. Moreover, concentrations of Lp-PLA2 were assessed in relation to the general characteristics of the study participants and the results of liver biopsy., Results: Concentrations of Lp-PLA2 were significantly higher in patients with definite NASH (161.8±0.9 μg/L, P<0.001), borderline NASH (135.4±47.7 μg/L, P=0.001), and simple fatty liver (132.4±46.2 μg/L, P=0.042) compared with healthy controls (86.2±40.7 μg/L). Furthermore, the serum Lp-PLA2 level was strongly associated to histological steatosis scores in patients with NAFLD (β=0.32, t=2.50, P=0.016)., Conclusion: Although subject to future confirmation, our data suggest that Lp-PLA2 levels are elevated in NAFLD.

Background: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MS). However, not all patients with the MS will develop NAFLD and not all patients with NAFLD have the MS. We sought to investigate the differences between patients with biopsy-proven NAFLD with and without the MS., Methods: A total of 357 consecutive patients with biopsy-proven NAFLD were analysed. Of them, 216 patients had nonalcoholic steatohepatitis (NASH) and 96 a fibrosis score ≥ 2. The MS was defined as ≥ 3 of the ATP III criteria., Results: A total of 214 patients with NAFLD met the criteria for the MS, while the remaining 143 did not. In NAFLD patients with the MS, homeostasis model of insulin resistance (P = 0·03; OR, 1·06; 95% CI, 1·023-1·25 per unit increase) and diabetes (P = 0·01; OR, 1·2; 95% CI, 1·1-2·4) were independent predictors of NASH. In NAFLD patients without the MS, the only variable independently associated with NASH was haemoglobin (P = 0·007; OR, 1·9; 95% CI, 1·4-3·6 per 50 g/L increase). Alanine aminotransferase (P = 0·03; OR, 1·04; 95% CI, 1·006-1·11 per 10 U/L increase) was an independent predictor of fibrosis ≥ 2 in NAFLD patients with the MS, while haemoglobin (P = 0·02; OR, 1·4; 95% CI, 1·2-1·9 per 50 g/L increase) was the only variable significantly associated with fibrosis ≥ 2 in NAFLD patients without the MS., Conclusions: Increased haemoglobin in NAFLD subjects without MS should be considered in the selection of cases for histological assessment., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: In this study, we aimed to investigate the relationship between the histological features of nonalcoholic fatty liver disease (NAFLD) and serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFBP-5) to determine the usefulness of this relationship in clinical practice., Materials and Methods: Serum samples were collected from 92 patients with biopsy-proven NAFLD and 51 healthy controls and serum levels of IGF-1 and IGFBP-5 were assayed by enzyme-linked immunosorbent assay., Result: Serum IGFBP-5 levels were correlated with liver steatosis, fibrosis, and nonalcoholic steatohepatitis scores. IGF-1 levels were significantly decreased in patients with moderate-to-severe fibrosis compared with patients with no or mild fibrosis., Conclusion: Serum IGFBP-5 levels may be useful to differentiate both advanced fibrosis and definite nonalcoholic steatohepatitis from other NAFLD groups. Also, serum IGF-1 levels may be useful to differentiate advanced fibrosis in patients with NAFLD.

Background/Aims. The aim of this study was to compare the effects of ursodeoxycholic acid (UDCA) alone and UDCA plus domperidone on dissolution of solitary or multiple gallstones. Methods. Fifty-three patients with cholesterol gallstones were randomized into three treatment groups: group I (n = 22) was given UDCA (15 mg/kg/day) alone and group II (n = 18) was treated with domperidone (30 mg/day) in addition to UDCA. The control group (n = 13) was followed without a medical treatment. Gallbladder volumes and ejection fractions were measured sonographically in all patients before and after treatment. Results. After 12 months of treatment, stone dissolution was found in 9 (40.9%) of the patients in group I and 7 (38.8%) of the patients in group II. The difference was statistically significant compared to controls in both treatment groups (P < 0.05) but the two groups did not show a difference between each other (P > 0.05). All the patients that achieved dissolution had multiple gallstones except for one patient with a solitary stone in group I. Neither monotherapy of UDCA nor the combination with domperidone affected the ejection fraction of gallbladder. Conclusions. Combination with domperidone did not potentiate the efficacy of UDCA. It has been observed that both UDCA alone and UDCA plus domperidone treatment did not affect ejection fraction of gallbladder.

Aim: In this study, we aimed to investigate the relationship between the histological fibrosis stage of nonalcoholic fatty liver disease (NAFLD) and serum connective tissue growth factor (CTGF) to determine the usefulness of this relationship in clinical practice., Methods: Serum samples were collected from 51 patients with biopsy-proven NAFLD and 28 healthy controls, and serum levels of CTGF were assayed by ELISA., Results: Levels of CTGF were significantly higher in patients with NAFLD compared with controls (P=0.001). The serum CTGF levels were significantly increased, that correlated with histological fibrosis stage, in patients with NAFLD [in patients with no fibrosis (stage 0) 308.2 ± 142.9, with mild fibrosis (stage 1-2) 519.9 ± 375.2 and with advanced fibrosis (stage 3-4) 1353.2 ± 610 ng/l, P < 0.001]. Also serum level of CTGF was found as an independent predictor of histological fibrosis stage in patients with NAFLD (β = 0.662, t=5.6, P <0.001). The area under the ROC curve was estimated 0.931 to separate patients with severe fibrosis from patients with other fibrotic stages., Conclusion: Serum levels of CTGF may be a clinical utility for distinguishing NAFLD patients with and without advanced fibrosis.

Background: Increased serum concentrations of pigment epithelium-derived factor (PEDF) have been linked to the metabolic syndrome in the general population. However, the relationship between serum PEDF and nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, remains unknown., Methods: We assayed serum PEDF levels in 156 patients with biopsy-proven NAFLD and 103 nonsteatotic control subjects who were matched for age and sex. The association between levels of PEDF and clinical, biochemical, and histological phenotypes was examined., Results: NAFLD patients had significantly higher serum PEDF levels (1.97±0.50 μg/mL) than control subjects (1.51±0.49 μg/mL, Student's t test, P<0.001). Multivariable-adjusted stepwise regression analysis showed that PEDF ([beta]=0.32, t=3.13, P=0.002) and triglycerides ([beta]=0.22, t=2.23, P=0.02) were, in the order they entered into the model, the main independent predictors of steatosis scores in our patients with NAFLD., Conclusions: Serum PEDF levels are significantly increased in patients with biopsy-proven NAFLD and are associated with liver steatosis independently of traditional risk factors., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background/aims: Fibrinogen-like protein 2 (fgl2), has recently been identified as a new member of the fibrinogen-like family of proteins. In this study we assayed plasma levels of fgl2 in patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) and examined their association with clinical, biochemical and histological phenotypes., Methodology: Levels of plasma fgl2 were measured by enzyme linked immunosorbent assay and compared between the study groups. Moreover, concentrations of fgl2 were assessed in relation to the general characteristics of the study participants and the results of the liver biopsy., Results: Levels of fgl2 were significantly higher in patients with definite non-alcoholic steatohepatitis (NASH) (788±190pg/mL, p<0.001) and borderline NASH (710 ± 140pg/mL, p<0.001) compared with controls (515±174pg/mL). No significant differences were found in patients with simple steatosis (649 ± 162pg/mL) as compared with controls. There were no associations between the plasma fgl2 levels with the fibrosis stage and steatosis grade., Conclusions: Although subject to future confirmation, our data suggest that fgl2 levels are elevated in the more severe forms of NAFLD.

Background: Research suggests the presence of mild-to-moderate iron overload in patients with nonalcoholic fatty liver disease (NAFLD). The role played by hepcidin, the master regulatory hormone of systemic iron metabolism, in the pathogenesis of NAFLD remains controversial. The aims of this study were to: (1) Evaluate serum hepcidin levels in patients with biopsy-proven NAFLD and age- and sex-matched controls and (2) identify the potential associations of hepcidin with the clinical and biochemical characteristics of the study participants., Methods: Serum levels of hepcidin were measured by enzyme-linked immunosorbent assay and compared in 88 patients with NAFLD (56 males and 32 females; mean age, 44 ± 11 years) and 88 controls (51 males and 37 females; mean age, 43 ± 12 years). Moreover, concentrations of hepcidin were assessed in relation to the general characteristics of the study participants and the results of liver biopsy., Results: Serum levels of hepcidin were significantly higher in patients with NAFLD (63.5 ± 19.5 ng/mL, P<0.001) compared with controls (32.7 ± 8.3 ng/mL). Multivariable regression analyses in patients with NAFLD showed that hepcidin levels were positively associated with total cholesterol (β=6.9, t=3.3, P<0.01) and triglycerides (β=1.4, t=2.4, P<0.05), but not with iron parameters, histological staging, and pathological characteristics of NAFLD., Conclusions: Although subject to future confirmation, our data suggest that hepcidin levels are elevated in NAFLD and could be associated with lipid parameters in this setting.

Sirtuins are members of the silent information regulator 2 (Sir2) family, a group of Class III histone/protein deacetylases. There are 7 different sirtuins in mammals (SIRT1-7), of which SIRT1 is the best known and most studied. SIRT1 is responsible for the regulation of protein activation by means of deacetylating a variety of proteins that play important roles in the pathophysiology of metabolic diseases. Recently, it has been shown that SIRT1 plays key roles in the regulation of lipid and glucose homeostasis, control of insulin secretion and sensitivity, antiinflammatory effects, control of oxidative stress and the improvements in endothelial function that result due to increased mitochondrial biogenesis and β-oxidation capacity. Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease, and it has been accepted as the hepatic component of metabolic syndrome. Recent studies have shown that SIRT expression in the liver is significantly decreased in an NAFLD model of rats fed a high-fat diet, and moderate SIRT1 overexpression protects mice from developing NAFLD. In addition to resveratrol, a natural SIRT1 activator, small-molecule pharmacologic SIRT1 activators have positive effects on metabolic diseases. These effects are particularly promising in the case of diabetes mellitus, for which phase studies are currently being performed. With this information, we hypothesized that the pharmacologic activation of SIRT1, which has been implicated in the pathogenesis of NAFLD, will be a potential therapeutic target for treating NAFLD. In this paper, we review the metabolic effects of SIRT1 and its association with the pathophysiology of NAFLD.

Background: The stomach is regarded as a rare site for metastasis. When a gastric mass is observed macroscopically, the presumed diagnosis is usually a primary gastric carcinoma. However, the stomach may be involved in metastatic malignant melanoma. Besides a possible macroscopical misdiagnosis, metastatic gastric melanoma may also be misdiagnosed microscopically as adenocarcinoma due to its protean histological characteristics. These features make metastatic gastric melanoma a challenging diagnosis in some cases., Case Report: We report a patient with metastatic gastric melanoma referred to us with an initial macroscopic and histopathological diagnosis of primary gastric adenocarcinoma. He was diagnosed as having metastatic gastric melanoma by further examination because of the peculiar metastatic involvement and normal gastrointestinal tumor marker levels., Conclusions: The stomach may be involved in melanoma and melanoma metastasis to the stomach is a diagnosis that should be taken into account while evaluating any gastric mass lesion. It is likely to be encountered more commonly nowadays due to the significant increase in the melanoma incidence. A history of melanoma, an atypical metastatic pattern, and normal gastrointestinal tumor marker levels may contribute to its diagnosis.

Background: Breast metastasis is an extremely rare phenomenon. While nearly every malignancy has been described to metastasize to the breast; melanoma, lymphoma and leukemia tend to be the most common. Among these primary tumors, melanoma metastasis represents a diagnostic pitfall for both the clinicians and histopathologists., Methods: We report a case of widely metastatic malignant melanoma with diagnostic difficulties in both clinical and histopathological evaluation. Thorax CT, Abdominal MRI, tumor marker screening and two biopsies were performed to conclude the primary., Results: In clinical evaluation, there were rapidly proliferating multiple nodular lesions at the skin, breasts, lungs, ovaries and peritoneum accompanied by only increased CA 125 in tumor marker panel. The initial biopsy performed from a skin nodule was concordant with a metastatic carcinoma suggesting breast as the primary. The diagnosis was made by immunohistochemical staining of the second biopsy performed from a breast nodule., Conclusion: Although no strict clinical criteria exist to differentiate a melanoma metastasis to the breast from a primary breast carcinoma atypically rapid growth, normal Ca 15-3 level, and a history of prior melanoma may be helpful. However, it may be still misdiagnosed in some cases even histopathologically if the immunohistochemical staining is not performed.