Securing wider EU commitment to the elimination of hepatitis C virus.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programmes-from the municipality level to the EU level-were launched, resulting in an overall decrease in viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct-acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the third EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and reported the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Securing sustainable funding for viral hepatitis elimination plans.

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct-acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries' health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro-elimination approach in specific populations is less complex and less costly than country-wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO.

A micro-elimination approach to addressing hepatitis C in Turkey.

BACKGROUND: In 2016, WHO passed the Global Health Sector Strategy on Viral Hepatitis (GHSS), calling for its elimination by 2030. Two years later, Turkey approved a strategy to reach the WHO targets. This study reports new national prevalence data, breaks it down by subpopulation, and models scenarios to reach HCV elimination. METHODS: Literature was reviewed for estimates of HCV disease burden in Turkey. They were discussed with stakeholders and used as inputs to develop a disease burden model. The infected population was estimated by sequelae for the years 2015-2030. Three scenarios were developed to evaluate the disease burden in Turkey: a Base 2017 scenario, representing the current standard of care in Turkey; an increased treatment scenario, representing the impact of improved access to DAAs; and a WHO targets scenario, which meet the WHO GHSS viral hepatitis targets of a 65% reduction in mortality and 90% diagnosis rate of the infected population by 2030. RESULTS: At the beginning of 2017, 271,000 viremic infections were estimated. Of these, 58,400 were diagnosed and 10,200 treated. Modelling results showed that, with the current treatment paradigm in Turkey, by 2030 the total number of viremic HCV infections would decline by 35%, while liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis would decrease by 10-25%. In the increased treatment scenario, by 2030 viremic HCV infections would decrease by 50%; liver-related deaths, HCC and decompensated cirrhosis would decrease by 45-70%. In the WHO targets scenario, HCV infections would decrease by 80%; sequelae would decrease by 80-85%. Data on disease burden in micro-elimination target subpopulations are largely unavailable. CONCLUSIONS: To meet the WHO Global Health Sector Strategy targets for the elimination of HCV, Turkey needs to increase treatment. Better data are needed as well as countrywide access to DAAs.

Gut Microbiome and Gastrointestinal Cancer: Les liaisons Dangereuses.

Gastrointestinal (GI) cancers are the leading cause of mortality worldwide. These cancers are the end result of a complex interplay between gene and environment. Bacteria, parasites, and viruses have been implicated in some cancers. Recent data have put at focus the gut microbiome as the key player firing tumorigenesis. Experimental and human studies have provided evidence on the role of microbiota in cancer development. Although subject to changes in different settings such as antibiotic treatment, diet or lifestyle, our microbiome is quite stable and is capable of increasing susceptibility to cancer or decrease and halt its progression. The crucial event in carcinogenesis triggered by microbiome seems to be chronic inflammation influencing the genomic stability of host cells and activating immune mechanisms. Infection-related cancers represent 5.5% of the global cancer burden. Chronic inflammation predisposes to cancer in various GI organs, including hepatocellular carcinoma caused by hepatitis B or hepatitis C virus-related chronic hepatitis, gastric cancer (GC) caused by Helicobacter pylori-associated chronic gastritis, colorectal cancer caused by inflammatory bowel disease, bile duct cancer by primary sclerosing cholangitis, and esophageal cancer caused by Barrett esophagus. Apart from its impact in GI cancer development microbiota can also play an important role in the progression of cancer, response to chemotherapy or cancer prevention. In this review we will discuss the role of microbiome in GI cancers in the light of the current literature and the possible therapeutic options targeting microbiota in the near future.

Diet, microbiota, and colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world causing nearly 500,000 deaths every year. In addition to genetic background, environmental factors including diet and lifestyle are accepted as major contributors to adenoma and CRC development. Lifestyle factors include high BMI, obesity, and reduced physical activity. Growing interest and accumulating data on human microbiota implicate that host-microbe interplay has an important role in the development of metabolic, neoplastic, and inflammatory diseases. Findings from recent studies suggest that colon cancer risk is determined by the interaction between diet and gut microbiota. Dietary changes affect gut microbiota and conversely microbiota mediates the generation of dietary factors triggering colon cancer. Identification of the microbial communities associated with carcinogenesis is of crucial importance. Nowadays, with the evolvement of culture-independent molecular techniques, it has become possible to identify main bacterial species in healthy individuals, inflammatory conditions, and CRC. Some recent studies have shown the differences in intestinal microbiota between colon cancer patients and healthy individuals. Animal studies have provided a better understanding of interaction between pathobionts and symbionts in the development of colon cancer. There is no single causative organism identified in CRC; however, there is strong evidence that reduction of protective bacteria, increase in some bacteria (ie, fusobacterium members; Bacteroides/Prevotella), and age-related changes in microbiota have an impact on adenoma or cancer development. Future studies will enable us to understand procarcinogenic and anticarcinogenic mechanisms and give insights to rational manipulation of the microbiota with prebiotics, probiotics, or dietary modifications.

Being a Female Gastroenterologist in Turkey.

BACKGROUND/AIMS: Our aim is to examine the representation of woman gastroenterologists in both work and social life in Turkey and to elucidate the difficulties they encounter during their career pathways or while actively practicing their profession. MATERIALS AND METHODS: A self-structured survey consisting of 25 questions was sent via email to all 152 female gastroenterologists. Survey results were received from 140 participants. RESULTS: Sixty percent of the woman gastroenterologists had marriage-career conflicts, and 74% of them stated that they could not manage work-life balance with their children. Among these woman gastroenterologists, 46.6% of them reported that they had faced carrier-related barriers and challenges while applying for an academic rise or expecting a promotion in their job, 58.5% were exposed to gender mobbing, and 35.6% were subjected to verbal or physical violence. On the other hand, woman gastroenterologists are found to be underrepresented in endoscopic interventions where only one-third of the participants perform invasive endoscopic procedures, and the percentage of those who perform advanced endoscopy such as endoscopic submucosal dissection and endoscopic mucosal resection remains even less as 8.9%. The number of women in leadership positions during their careers is found to be low, and only 2 women were selected as the president of the society since 1959, the establishment time of the Turkish Society of Gastroenterology. CONCLUSION: More effort is needed to keep a fair gender balance in Turkish gastroenterology society and to increase the women's representation in therapeutic endoscopy options and also in leadership positions.

IgG-based elimination diet in migraine plus irritable bowel syndrome.

OBJECTIVES: To evaluate therapeutic potential of the immunoglobulin G (IgG)-based elimination diet among migraine patients with irritable bowel syndrome (IBS). BACKGROUND: Food elimination has been suggested as an effective and inexpensive therapeutic strategy in patients with migraine and concomitant IBS in the past studies. METHODS: A total of 21 patients (mean [standard deviation] age: 38.0 [11.2] years; 85.7% females) diagnosed with migraine and IBS were included in this double-blind, randomized, controlled, cross-over clinical trial composed of baseline (usual diet), first diet (elimination or provocation diets), and second diet (interchange of elimination or provocations diets) phases and 4 visits. RESULTS: IgG antibody tests against 270 food allergens revealed mean (standard deviation) reaction count to be 23.1 (14.1). Compared with baseline levels, elimination diet per se was associated with significant reductions in attack count (4.8 [2.1] vs 2.7 [2.0]; P < .001), maximum attack duration (2.6 [0.6] vs. 1.4 [1.1] days; P < .001), mean attack duration (1.8 [0.5] vs. 1.1 [0.8] days; P < .01), maximum attack severity (visual analog scale 8.5 [1.4] vs. visual analog scale 6.6 [3.3]; P < .001), and number of attacks with acute medication (4.0 [1.5] vs. 1.9 [1.8]; P < .001). There was a significant reduction in pain-bloating severity (1.8 [1.3] vs. 3.2 [0.8]; P < .05), pain-bloating within the last 10 days (3.2 [2.8] vs. 5.5 [3.1]; P < .05), and improvement obtained in quality of life (3.6 [1.4] vs. 2.9 [1.0]; P < .05) by the elimination diet as compared with provocation diet. CONCLUSIONS: Our findings indicate that food elimination based on IgG antibodies in migraine patients who suffer from concomitant IBS may effectively reduce symptoms from both disorders with possible positive impact on the quality of life of the patients as well as potential savings to the health-care system.

Rare association of solitary necrotic nodule of the liver with rheumatoid arthritis and systemic lupus erythematosus.

Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion with uncertain etiology characterized by a "completely necrotic core" and a hyalinized capsule containing elastin fibers (Journal of Clinical Pathology 36:1181-1183, 1983). We report herein a 26-year-old woman with a previous diagnosis of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome and no history of malignancy who presented with a complaint of diarrhea of 1-year duration. In the abdominal ultrasound, multiple paraaortic, portocaval, and ileal lymphadenopathies (LAPs) have been found with the largest one being 2 cm in size. The biopsy of the iliac LAP showed reactive nodular hyperplasia. An abdominal CT disclosed an incidental hypoechoic, heterogenous mass sized 27 × 27 mm close to segment VI of the liver. A trucut biopsy of this lesion was made, and clinicopathologic features of the specimen were compatible with a solitary necrotic nodule of the liver. Here, we discuss the diagnosis and the clinical course of this rare entity in light of current literature.

Risk factors for laryngopharyngeal reflux.

The aim of this study was to evaluate the demographic and clinicopathologic characteristics of gastroesophageal reflux disease (GERD) with and without laryngopharyngeal reflux (LPR) to determine the risk factors for the occurrence of LPR in patients with GERD. This is a retrospective study of GERD patients with and without LPR. From the outpatient computer program of our hospital we randomly enrolled 45 GERD patients with LPR into the first group and another 45 GERD patients without LPR to the second group. Medical records of the patients in both groups were examined. All patients underwent upper gastrointestinal system endoscopy. LPR was confirmed by laryngoscopy, and LPR-related laryngoscopy scoring. Non-erosive GERD (NERD), erosive GERD (ERD) and Barrett's esophagus (BE) were diagnosed by endoscopy and histopathology. Various clinical parameters including status of Helicobacter pylori (H. pylori) infection, topography of gastritis were analyzed. For therapy, lansoprazole in a dosage of 30 mg BID for at least 8 weeks were given to all patients in both groups. GERD patients with and without LPR were compared according to demographic, clinic, endoscopic and histopathological parameters. The results revealed that patients with LPR were younger than the patients without LPR (38.7 ± 10.2 years and 43.8 ± 11.5 years; p = 0.08); however, there was no statistical significance. Patients without LPR showed no gender predilection (55% male) while LPR patients showed male preponderance (71% male). In LPR group, 11 patients (24%) had NERD, while 28 (62%) and 6 (13%) patients had ERD and BE, respectively. Twenty-seven (60%) patients without LPR were diagnosed as NERD, 15 patients (33%) without LPR had ERD and only 3 patients (6.6%) showed the histological findings of BE. The patients in LPR group had higher body mass index. Hiatal hernia was more frequent in the patients with LPR (53%) than in the patients without LPR (24%) (p = 0.005). LPR patients had longer duration of reflux symptoms than the patients without LPR (p = 0.04). H. pylori status was not different in both groups but the patients without LPR had more corpus gastritis than the patients with LPR. Eight weeks of lansoprazole treatment was successful in 71% of patients with LPR, and 86% of patients without LPR. We concluded that male gender, hiatal hernia, longer duration of symptoms, high BMI, having ERD and BE seems as risk factors for the occurrence of LPR in patients with GERD. H. pylori status did not have any effect on the development of LPR. Corpus dominant gastritis may have a protective role against the development of LPR. Proton pump inhibitor therapy is less effective in patients with LPR.

A New Risk-Scoring System for Colorectal Cancer and Polyp Screening by Turkish Colorectal Cancer and Polyp Study Group.

BACKGROUND: Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screen- ing tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer. METHODS: We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index, polyp incidence, polyp size, number and localization, and pathologic findings were recorded. RESULTS: The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81%, specificity 40%, positive predictive value 25.68%, and negative predictive value 89.84%, for adenomatous polyp detection; and sensitivity 96%, specificity 39%, positive predictive value 3.35%, negative predictive value 99.29%, for colorectal cancer detection. CONCLUSION: Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score ≥ 4 must be included in the screening tests for colorectal cancer.

Optimizing the Personalized Care for the Management of Rectal Cancer: A Consensus Statement.

Colorectal cancer is the third most common cancer in Turkey. The current guidelines do not provide sufficient information to cover all aspects of the management of rectal cancer. Although treatment has been standardized in terms of the basic principles of neoadjuvant, surgical, and adjuvant therapy, uncertainties in the management of rectal cancer may lead to significant differences in clinical practice. In order to clarify these uncertainties, a consensus program was constructed with the participation of the physicians from the Acibadem Mehmet Ali Aydinlar and Koç Universities. This program included the physicians from the departments of general surgery, gastroenterology, pathology, radiology, nuclear medicine, medical oncology, radiation oncology, and medical genetics. The gray zones in the management of rectal cancer were determined by reviewing the evidence-based data and current guidelines before the meeting. Topics to be discussed consisted of diagnosis, staging, surgical treatment for the primary disease, use of neoadjuvant and adjuvant treatment, management of recurrent disease, screening, follow-up, and genetic counseling. All those topics were discussed under supervision of a presenter and a chair with active participation of related physicians. The consensus text was structured by centralizing the decisions based on the existing data.

Time course of collagen peak in bile duct-ligated rats.

BACKGROUND: One of the most useful experimental fibrogenesis models is the "bile duct-ligated rats". Our aim was to investigate the quantitative hepatic collagen content by two different methods during the different stages of hepatic fibrosis in bile duct-ligated rats on a weekly basis. We questioned whether the 1-wk or 4-wk bile duct-ligated model is suitable in animal fibrogenesis trials. METHODS: Of the 53 male Wistar rats, 8 (Group 0) were used as a healthy control group. Bile duct ligation (BDL) had been performed in the rest. Bile duct-ligated rates were sacrificed 7 days later in group 1 (10 rats), 14 days later in group 2 (9 rats), 21 days later in group 3(9 rats) and 28 days later in group 4 (9 rats). Eight rats underwent sham-operation (Sham). Hepatic collagen measurements as well as serum levels of liver enzymes and function tests were all analysed. RESULTS: The peak level of collagen was observed biochemically and histomorphometricly at the end of third week (P < 0.001 and P < 0.05). Suprisingly, collagen levels had decreased with the course of time such as at the end of fourth week (P < 0.01 and P < 0.05). CONCLUSION: We have shown that fibrosis in bile duct-ligated rats is transient, i.e. reverses spontaneously after 3 weeks. This contrasts any situation in patients where hepatic fibrosis is progressive and irreversible as countless studies performed by many investigators in the same animal model.

Hepatocellular Cancer and Gut Microbiome: Time to Untie Gordian's Knot.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide and the incidence is growing on a global scale. About 90% of cases develop on the cirrhotic liver and the etiology is multifactorial. Increasing number of studies suggest that gut microbiota influences the development and progression of liver diseases, including chronic hepatic inflammation, fibrosis, cirrhosis, and HCC. The key role of gut microbiota in carcinogenesis seems to be associated with genomic instability of host cells and immune dysregulation. Recent clinical studies showed that a stable and healthy microbiota initially could have the ability to resist the emergence of chronic inflammation and, therefore, prevent the induction of carcinogenic cells in various organs such as the esophagus, stomach, colon, and liver. The progression from inflammation to cancer is a stepwise process occurring by the concerted action of several factors such as dysbiosis, increased gut permeability, diet, metabolomic, genetic, and epigenetic changes. In this article, we aimed to review the possible role of gut microbiota in the development, progression, and treatment of HCC.

Subtracted Adulthood Mass Index - a new index to predict NAFLD risk in non-obese individuals.

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease. The aims of the current study are to determine the relationship between NAFLD in non-obese individuals and weight gain during adulthood and develop a new index for the identification of NAFLD risk. Materials and Methods: For this cross-sectional study, 362 patients who underwent abdominal ultrasonography (USG) in our clinic were included. Seventy-eight individuals were obese (>30 kg/m2). A history of weight gain during adulthood and systemic metabolic diseases was collected at the time of the study. A new index termed "Subtracted Adulthood Mass Index" (SAMI) was created to estimate the risk of NAFLD development for non-obese people. SAMI is the ratio of the difference between the individual's current weight and his/her weight at 20 years old to his/her height squared (kg/m2). Results: When the SAMI cut-off was set at 3 kg/m2, the sensitivity for predicting NAFLD risk was 85.2%, the specificity was 66.9%, the PPV was 79.1%, and the NPV was 75.4%. Conclusion: In this innovational study, a new index named SAMI was developed to identify non-obese people who are at risk of developing NAFLD. The SAMI is easy to calculate and appropriate for clinical use.

The Changing Prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Turkey in the Last Decade.

BACKGROUND/AIMS: The true prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) is unknown in Turkey due to a lack of population-based studies. The aim of this study was (i) to determine the overall and region-specific prevalence of NAFLD in Turkey; (ii) to analyze the factors associated with the prevalence; and (iii) to determine the nationwide change in the prevalence of NAFLD in the last decade. MATERIALS AND METHODS: The 10-year data (2007 to 2016) of 113,239 apparently healthy subjects visiting the check-up clinics of Acibadem Hospitals Group were retrospectively analyzed. A subgroup of patients (n=8120) statistically representing the bigger cohort were selected. The prevalence was analyzed according to ultrasound findings, age, sex, body mass index (BMI), geographical region, and time periods trisected as 2007-2010, 2011-2013 and 2014-2016. RESULTS: The overall prevalence of NAFLD in Turkey was found to be 48.3%. It was highest among people >50 years of age (65.6%), male sex (64.0%), with a BMI>25 kg/m2 (63.5%) and in Central and Eastern Anatolia regions (57.1% and 55.7%, respectively). The prevalence of NAFLD was 43.5% between 2007-2010, 47.6% between 2011-2013 and 53.1% between 2014-2016 and the rate of increase was 22%. Multivariate analysis showed that male sex, serum alanine aminotransferase (ALT) level, older age, BMI, type-II diabetes mellitus, hypertension and dyslipidemia were independent factors associated with NAFLD. CONCLUSION: NAFLD is a highly prevalent disease affecting almost half of the Turkish population (48.3%). We are faced with a dramatic increase in NAFLD prevalence in the past 10 years.

The crosstalk between H. pylori virulence factors and the PD1:PD-L1 immune checkpoint inhibitors in progression to gastric cancer.

BACKGROUND: The progression to gastric cancer has been linked to chronic infection with Helicobacter pylori (H. pylori). Immune checkpoint inhibitors (programmed cell death -1, PD-1; programmed cell death -ligand 1, PD-L1) have a role in cancer immune escape. The relationship between H. pylori virulence factors with PD-1, PD-L1 T helper 1 (Th1), T helper 17 (Th17), and regulatory T cell (Treg) response genes, has not been thoroughly investigated in the development of gastric cancer. Therefore, we evaluated how H. pylori virulence factors influence the expression levels of immune-related genes in the development of gastric immunopathology. METHODS: A total of 92 gastric tissues of normal controls and patients with gastritis, gastric ulcer, and gastric cancer were examined for the expression of immune-checkpoint inhibitor genes (PD-1 PD-L1), Th1 (interferon- γ, IFN-γ), Th17 (interleukin- 17, IL-17, Retinoic-acid-receptor- related orphan nuclear receptor gamma t, RORγ-t), and Treg (Forkhead box P3, FOXP3) response genes with quantitative real-time PCR (qRT-PCR). Furthermore, correlation of H. pylori virulence factors' (cytotoxin-associated gene A, cagA; vacuolating cytotoxin gene A, vacA (s1,s2,m1,m2); blood group antigen-binding adhesin gene A, babA, duodenal ulcer promoting gene A, dupA; the putative neuraminyllactose-binding hemagglutinin homolog, hpaA; neutrophil-activating protein A napA; outer inflammatory protein A, oipA; urease A, ureA; and urease B, ureB) genotypes with a degree of inflammation and density of H. pylori were investigated. Next, the relationship between H. pylori virulence factors and immune-checkpoint inhibitor genes, and T-cell response genes was evaluated. Eventually, a decision tree model was developed to determine the clinical outcome of patients using expression data. RESULTS: The intensity of PD-1 and PD-L1 mRNA expression was increased significantly in gastric tissue of patients with gastric ulcer (PD-1: 2.3 fold, p=0.01; PD-L1: 2.1 fold, p=0.004), and gastric cancer (PD-1: 2 fold, p= 0.04; PD-L1: 1.8 fold, p=0.05) compared with control subjects. Also, PD-1: PD-L1 expression was significantly higher in patients with gastritis, who were infected with a marked density of H. pylori compared with its mildly infected counterparts. Furthermore, a novel negative correlation was found between PD-1 (r= -0.43) and PD-L1 (r= -0.42) with FOXP3 in patients with gastritis. CagA-positive H. pylori strain's negative association with PD-L1 expression (r=-0.34) was detected in patients with gastritis. Interestingly, PD-1 mRNA expression correlated positively with vacA s2/m2, in gastritis (r=0.43) and ulcer (r=0.43) patients. Furthermore, PD-1: PDL1 expression negatively correlated with vacA m1/m2 (r=-0.43 for PD-1; r=-0.38 for PD-L1) in gastritis patients. Moreover, an inverse correlation of PDL1 was present with vacA m1 (r=0.52) and vacA s1/m1 (r=0.46) versus vacA m2 (r=-0.44) and vacA m1 (r=0.52) and vacA s1/m2 (r=-0.14) in ulcer patients, respectively. Also, a correlation of vacA m2 (r=-0.47) and vacA s1/s2 (r= 0.45) with PD-1 was detected in ulcer patients. In addition, a novel negative correlation between FOXP3 mRNA levels and napA was shown in patients with gastritis and ulcer (r=-0.59). Finally, a computer-based model that was developed showed that knowing the expression levels of PD-L1, RORγ-t, and vacA s1/m2 would be useful to detect the clinical outcome of a patient. CONCLUSION: Our results suggested that PD-1:PD-L1 immune checkpoint inhibitors were increased in gastric pre-cancerous lesions that progress to gastric cancer. Herein, we report the relationship between H. pylori virulence factors and expression of host immune checkpoint inhibitors for diagnostic prediction of gastric malignancies using computer-based models.

Determination of the upper limits of normal serum alanine aminotransferase (ALT) level in healthy Turkish population.

Background and Aim: Recent studies have reported that the widely accepted range of upper limits of normal (ULN) alanine aminotransferase (ALT) levels (ULN<40U/L) is high for the healthy population. We aimed to find the correct ULN level for men and women in a presumed healthy liver population group. Materials and Methods: The data of 7410 healthy subjects visiting the check-up clinics were retrospectively analysed in this study. Patients were divided in to "healthy liver group" (n=2694) and "high-risk liver group" (n=4716) based on fatty liver on ultrasound, existing of chronic liver disease, ongoing significant alcohol consumption, diabetes mellitus and dyslipidaemia. Receiver operating characteristic (ROC) curves were generated and the area under the curve (AUC) was calculated at the 95th percentiles for both men and women. Results: The AUC score of ALT for men was 0.92, and the ULN for the serum ALT in men was found as 32.10 U/L (sensitivity of 0.89, specificity 0.85). The AUC score of ALT for women was 0.90, and the ULN for serum ALT was found as 23.15 U/L (sensitivity of 0.90, the specificity of 0.88). Conclusion: ULN for serum ALT level should be lowered and different cut-off values should be used for men (32.10 U/L) and women (23.15 U/L).

Regular coffee intake improves liver enzyme levels and liver histology in patients with chronic alcohol consumption, non-alcoholic fatty liver and non-alcoholic steatohepatitis: Report of 259 cases.

Background and Aim: This study aims to investigate the effects of chronic coffee consumption (>5 years) and type of coffee in non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFLD) and patients who have regular alcohol consumption. Materials and Methods: In this study, 158 healthy individuals and 101 patients with histologically proven NASH were enrolled. The daily amount of coffee intake, amount of alcohol use and type of coffee were calculated for all patients. The degree of steatosis and fibrosis was analyzed by transient elastography and liver ultrasound in non-NASH and by liver biopsy in NASH patients. Results: Patients with a history of coffee consumption (n=132) had lower liver enzyme levels compared to the non-coffee group (n=127) (p=0.001). Serum ALT level was significantly lower [ALT: 21.2±11.7 U/L vs. 56.4±15.6 U/L (p=0.004)], and the liver histopathology was significantly better for patients with a coffee consumption of daily for >5years (p=0.045 for fibrosis score for NASH, p=0.036 for LSM and p=0.015 for CAP measurements for the non-NASH patient). Conclusion: Coffee seems to have a positive protective effect on liver histology and liver enzyme levels in healthy individuals, in patients with chronic alcohol consumption, NAFLD and NASH. These results are more prominent in patients who drink coffee on a regular daily base for more than five years.

Clinical characteristics of inflammatory bowel disease in Turkey: a multicenter epidemiologic survey.

AIM: To investigate the epidemiologic and clinical characteristics of inflammatory bowel disease (IBD) patients in a large multicenter, countrywide, hospital-based study in Turkey. MATERIALS AND METHODS: Twelve centers uniformly distributed throughout Turkey reported through a questionnaire the new IBD cases between 2001 and 2003. The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has been reported per 100,000 people. Epidemiologic features and clinical characteristics of both diseases were analyzed. RESULTS: During the study period, 661 patients of UC and 216 patients of CD were identified. The incidence in the referral population was 4.4/100,000 and 2.2/100,000 for UC and CD, respectively. The age of the patients showed the characteristic biphasic distribution with 2 peaks between 20 and 30 and 50 and 70 years. A male predominance was observed in both diseases. A history of smoking was detected in 15.5% of UC patients and 49.3% of patients with CD. Family history was positive in 4.4% in UC and 8.3% in CD patients. Concomitant amebiasis was observed in 17.3% of patients with UC and 1.3% of patients with CD. A history of appendectomy was reported in 15% of patients with CD and only 3% of patients with UC. Both extraintestinal and local complications were more frequent in CD patients, whereas arthritis was most common in both diseases. CONCLUSIONS: IBDs are frequently encountered in Turkey. IBD incidence is lower than North and West Europe but close to Middle East in our country. The majority of IBD cases are diagnosed in young people (20 to 40 y) with predominance in males. The rate of both intestinal and extraintestinal complications in our population was low when compared with the data reported in the literature. IBD and especially UC, can coexist with amebiasis or become manifest with amebic infestation. The presence of concomitant ameba may create confusion and cause dilemmas in the diagnosis and treatment of UC.