Activin-A causes Hepatic stellate cell activation via the induction of TNFα and TGFß in Kupffer cells.

BACKGROUND & AIMS: TGFß superfamily member Activin-A is a multifunctional hormone/cytokine expressed in multiple tissues and cells, where it regulates cellular differentiation, proliferation, inflammation and tissue architecture. High activin-A levels have been reported in alcoholic cirrhosis and non-alcoholic steatohepatitis (NASH). Our aim was to identify the cell types involved in the fibrotic processes induced by activin-A in liver and verify the liver diseases that this molecule can be found increased. METHODS: We studied the effect of activin-A on mouse primary Kupffer cells (KCs) and Hepatic Stellate cells (HSCs) and the levels of activin-A and its inhibitor follistatin in the serum of patients from a large panel of liver diseases. RESULTS: Activin-A is expressed by mouse hepatocytes, HSCs and Liver Sinusoid Endothelial cells but not KCs. Each cell type expresses different activin receptor combinations. HSCs are unresponsive to activin-A due to downregulation/desensitization of type-II activin receptors, while KCs respond by increasing the expression/production of TNFα και TGFß1. In the presence of KCs or conditioned medium from activin-A treated KCs, HSCs switch to a profibrogenic phenotype, including increased collagen and αSMA expression and migratory capacity. Incubation of activin-A treated KC conditioned medium with antibodies against TNFα and TGFß1 partially blocks its capacity to activate HSCs. Only patients with alcoholic liver diseases and NASH cirrhosis have significantly higher activin-A levels and activin-A/follistatin ratio. CONCLUSIONS: Activin-A may induce fibrosis in NASH and alcoholic cirrhosis via activation of KCs to express pro-inflammatory molecules that promote HSC-dependent fibrogenesis and could be a target for future anti-fibrotic therapies.

Screening for Hepatopulmonary Syndrome in Cirrhotic Patients Using Technetium 99m-macroaggregated Albumin Perfusion Lung Scan (Tc-MAA): Diagnostic Approach and Clinical Correlations.

BACKGROUND AND AIMS: The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. MATERIALS AND METHODS: Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). RESULTS: In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). CONCLUSIONS: HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.

Geoepidemiology of hepatocellular carcinoma in the island of Crete, Greece. A possible role of pesticides.

BACKGROUND & AIMS: Geoepidemiological data of hepatocellular carcinoma (HCC) are lacking. Crete has a genetically homogeneous population and is suitable for studies to identify a possible contribution of environmental factors in HCC. METHODS: Databases for HCC (316 cases), hepatitis B virus (HBV) (633) and hepatitis C virus (HCV) (392), constructed over the past 20 years in our Unit, were used. Data included place of birth and place of residence for the last 15 years. Hellenic Statistical Authority provided population statistics from 1980 to 2014. Time-spatial methods were applied in Gis-ArcMap 10 software. Spatial autocorrelation tests (Moran's index) detected differences between the spatial distribution to place of residence. Spatial density maps were created. Kriging Interpolation was applied, to produce prediction maps of HCC. RESULTS: Hepatitis C virus appears in areas of high prevalence while HBV is uniformly distributed. HCC is more prevalent in Eastern Crete. A spatial autocorrelation between HCC and either HCV (Moran's I = 0.88, P < 0.001) or HBV (I = 0.84, P < 0.02) was found as expected. However, there is a discrepancy in the South East of Crete, where a higher prevalence of HCC than expected was observed. This is an area where extensive use of pesticides in large green houses is practiced. CONCLUSIONS: Hepatocellular carcinoma is associated with the dispersion of HCV and HBVs. In an area with widespread use of pesticides, a higher than expected spatial distribution of HCC was detected.

Increased fracture risk assessed by fracture risk assessment tool in Greek patients with Crohn's disease.

BACKGROUND: The World Health Organization has recently developed the fracture risk assessment tool (FRAX) based on clinical risk factors and bone mineral density (BMD) for evaluation of the 10-year probability of a hip or a major osteoporotic fracture. The aim of this study was to evaluate the use of the FRAX tool in Greek patients with inflammatory bowel disease (IBD). METHODS: FRAX scores were applied to 134 IBD patients [68 Crohn's disease (CD); 66 ulcerative colitis (UC)] who underwent dual-energy X-ray absorptiometry scans at the femoral neck and lumbar spine during the period 2007-2012. Calculation of the FRAX scores, with or without BMD, was made through a web-based probability model used to compute individual fracture probabilities according to specific clinical risk factors. RESULTS: The median 10-year probability of a major osteoporotic fracture for IBD patients based on clinical data was 7.1%, and including the BMD was 6.2%. A significant overestimation with the first method was found (P = 0.01). Both scores with and without BMD were significantly higher in CD patients compared with UC patients (P = 0.02 and P = 0.005, respectively). The median 10-year probability of hip fracture based on clinical data was 0.8%, and including the BMD was 0.9%. The score with use of BMD was significantly higher in CD compared with UC patients (P = 0.04). CONCLUSIONS: CD patients have significantly higher FRAX scores and possibly fracture risk compared with UC patients. The clinical FRAX score alone seems to overestimate the risk of osteoporotic fracture in Greek IBD patients.

Iron as a therapeutic target in chronic liver disease.

It was clearly realized more than 50 years ago that iron deposition in the liver may be a critical factor in the development and progression of liver disease. The recent clarification of ferroptosis as a specific form of regulated hepatocyte death different from apoptosis and the description of ferritinophagy as a specific variation of autophagy prompted detailed investigations on the association of iron and the liver. In this review, we will present a brief discussion of iron absorption and handling by the liver with emphasis on the role of liver macrophages and the significance of the iron regulators hepcidin, transferrin, and ferritin in iron homeostasis. The regulation of ferroptosis by endogenous and exogenous mod-ulators will be examined. Furthermore, the involvement of iron and ferroptosis in various liver diseases including alcoholic and non-alcoholic liver disease, chronic hepatitis B and C, liver fibrosis, and hepatocellular carcinoma (HCC) will be analyzed. Finally, experimental and clinical results following interventions to reduce iron deposition and the promising manipulation of ferroptosis will be presented. Most liver diseases will be benefited by ferroptosis inhibition using exogenous inhibitors with the notable exception of HCC, where induction of ferroptosis is the desired effect. Current evidence mostly stems from in vitro and in vivo experimental studies and the need for well-designed future clinical trials is warranted.

Pathogenesis of Hepatocellular Carcinoma: The Interplay of Apoptosis and Autophagy.

The pathogenesis of hepatocellular carcinoma (HCC) is a multifactorial process that has not yet been fully investigated. Autophagy and apoptosis are two important cellular pathways that are critical for cell survival or death. The balance between apoptosis and autophagy regulates liver cell turnover and maintains intracellular homeostasis. However, the balance is often dysregulated in many cancers, including HCC. Autophagy and apoptosis pathways may be either independent or parallel or one may influence the other. Autophagy may either inhibit or promote apoptosis, thus regulating the fate of the liver cancer cells. In this review, a concise overview of the pathogenesis of HCC is presented, with emphasis on new developments, including the role of endoplasmic reticulum stress, the implication of microRNAs and the role of gut microbiota. The characteristics of HCC associated with a specific liver disease are also described and a brief description of autophagy and apoptosis is provided. The role of autophagy and apoptosis in the initiation, progress and metastatic potential is reviewed and the experimental evidence indicating an interplay between the two is extensively analyzed. The role of ferroptosis, a recently described specific pathway of regulated cell death, is presented. Finally, the potential therapeutic implications of autophagy and apoptosis in drug resistance are examined.

Treatment of portal vein thrombosis in cirrhosis: a multicenter real life cοhort study.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics. METHODS: This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used. RESULTS: Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047). CONCLUSIONS: In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.

Convolutional Neural Networks for Optical Discrimination Between Histological Types of Colorectal Polyps Based on White Light Endoscopic Images.

The objective of this study was to compare different convolutional neural networks (CNNs), as employed in a Python-produced deep learning process, used on white light images of colorectal polyps acquired during the process of a colonoscopy, in order to estimate the accuracy of the optical recognition of particular histologic types of polyps. The TensorFlow framework was used for Inception V3, ResNet50, DenseNet121, and NasNetLarge, which were trained with 924 images, drawn from 86 patients.

Increased serum activin-A differentiates alcoholic from cirrhosis of other aetiologies.

BACKGROUND: Activin-A is a molecule of the TGF superfamily, implicated in liver fibrosis, regeneration and stem cell differentiation. However, data on activins in liver diseases are few. We therefore studied serum levels of activin-A in chronic liver diseases. To identify the origin of activin-A, levels in the hepatic vein were also estimated. MATERIALS AND METHODS: Nineteen controls and 162 patients participated in the study: 39 with hepatocellular carcinoma (HCC: 19 viral associated and 20 alcohol associated), 18 with chronic hepatitis C (CHC), 47 with primary biliary cirrhosis (26 PBC stage I-II and 21 stage IV), 22 with alcoholic cirrhosis (AC, hepatic vein blood available in 16), 20 with HCV cirrhosis (hepatic vein blood available in 18) and 16 patients with alcoholic fatty liver with mild to moderate fibrosis but no cirrhosis. RESULTS: Activin-A levels were significantly increased (P < 0·001) in serum of patients with AC (median 673 pg/mL, range 449-3279), compared with either controls (149 pg/mL, 91-193) or patients with viral cirrhosis (189 pg/mL, 81-480), CHC (142 pg/mL, 65-559) PBC stage I-II (100 pg/mL, 59-597) and PBC stage IV (104 pg/mL, 81-579). Only patients with AC-associated HCC had significantly increased levels of activin-A (2403 pg/mL, 1561-7220 pg/mL). Activin-A serum levels could accurately discriminate AC from cirrhosis of other aetiologies and noncirrhotic alcoholic fatty liver with fibrosis. CONCLUSIONS: Increased serum levels of activin-A only in patients with alcohol-related cirrhosis or HCC suggest a possible role of this molecule in the pathophysiology of AC. Further research is warranted to elucidate its role during the profibrotic process and its possible clinical applications.

Primary biliary cirrhosis in a genetically homogeneous population: disease associations and familial occurrence rates.

BACKGROUND: Primary biliary cirrhosis (PBC) is a disease with genetic and environmental pathogenetic background. Chemicals, infectious agents, hormone therapy, reproductive history and surgical interventions have been implicated in the induction of PBC. Familial PBC has been documented in first degree relatives (FDR). Most cohort studies are genetically heterogeneous. Our study aimed to determine eventual lifestyle or disease associations and familial occurrence rates in a genetically homogeneous and geographically defined population of PBC patients. METHODS: 111 consenting PBC patients, were compared with 115 FDR and 149 controls matched for age, sex, Cretan origin and residence. All participants completed a questionnaire regarding demographics, lifestyle, medical, surgical and reproductive history. Significant variables on the univariate analysis were analyzed by multivariate analysis using a forward step-wise logistic regression model. RESULTS: Dyslipidaemia was found in 69.4% of patients, 60% of FDR and 40.9% of controls (p < 0.0001 and p = 0.003 respectively), autoimmune diseases in 36.9% of patients, 30.4% of FDR and 13.4% of controls (p < 0.0001 and p = 0.011 respectively). Hashimoto's disease (p = 0.003), Raynaud syndrome (p = 0.023) and Sjögren syndrome (p = 0.044) were significantly associated with PBC. On multivariate analysis statistically significant associations were found with primary educational level (AOR 2.304, 95% CI 1.024-5.181), cholecystectomy (AOR 2.927, 95% CI 1.347-6.362) and the presence of at least another autoimmune disease (AOR 3.318, 95% CI 1.177-6.22). Cancer history was more frequent in patients than in controls (p = 0.033). Familial PBC was found to be 9.9%. CONCLUSIONS: Dyslipidaemia and autoimmune diseases were significantly increased not only in patients as expected but also in their FDR. An increased prevalence of malignancies was found in patients. Primary educational level, cholecystectomy and the presence of at least another autoimmune disease were found as putative risk factors for PBC. No association was found with smoking, urinary tract infection or reproductive history. The reported high familial occurrence of PBC could imply screening with AMA of FDR with at least another autoimmune disease.

Hepatitis C virus: A critical approach to who really needs treatment.

Introduction of effective drugs in the treatment of hepatitis C virus (HCV) infection has prompted the World Health Organization to declare a global eradication target by 2030. Propositions have been made to screen the general population and treat all HCV carriers irrespective of the disease status. A year ago the new severe acute respiratory syndrome coronavirus 2 virus appeared causing a worldwide pandemic of coronavirus disease 2019 disease. Huge financial resources were redirected, and the pandemic became the first priority in every country. In this review, we examined the feasibility of the World Health Organization elimination program and the actual natural course of HCV infection. We also identified and analyzed certain comorbidity factors that may aggravate the progress of HCV and some marginalized subpopulations with characteristics favoring HCV dissemination. Alcohol consumption, HIV coinfection and the presence of components of metabolic syndrome including obesity, hyperuricemia and overt diabetes were comorbidities mostly responsible for increased liver-related morbidity and mortality of HCV. We also examined the significance of special subpopulations like people who inject drugs and males having sex with males. Finally, we proposed a different micro-elimination screening and treatment program that can be implemented in all countries irrespective of income. We suggest that screening and treatment of HCV carriers should be limited only in these particular groups.

The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity.

The HCC constitutes one of the most frequent cancers, with a non-decreasing trend in disease mortality despite advances in systemic therapy and surgery. This trend is fueled by the rise of an obesity wave which is prominent the Western populations and has reshaped the etiologic landscape of HCC. Interest in the nucleotide-binding domain leucine-rich repeat containing (NLR) family member NLRP3 has recently been revived since it would appear that, by generating inflammasomes, it participates in several physiologic processes and its dysfunction leads to disease. The NLRP3 inflammasome has been studied in depth, and its influence in HCC pathogenesis has been extensively documented during the past quinquennial. Since inflammation comprises a major regulator of carcinogenesis, it is of paramount importance an attempt to evaluate the contribution of the NLRP3 inflammasome to the generation and management of HCC. The aim of this review was to examine the literature in order to determine the impact of the NLRP3 inflammasome on, and present a hypothesis about its input in, HCC.

New considerations for colorectal cancer screening based on the demographic profile of colorectal cancer in a Greek population.

Colorectal cancer screening has long been recommended for middle age and older individuals. Recent evidence indicates increasing incidence and mortality among young adults. Therefore, the present study re-examined the current recommendations using an asymptomatic average-risk population screened by colonoscopy. A total of 716 participants of a wide age range were prospectively enrolled in an open-access endoscopic screening program based on self-referral. Comparisons between different age, gender and location groups, and receiver operating characteristic curves (ROC) curves for best age selection for detection of lesions were employed. Increased incidence of advanced lesions was observed in adults <50 years old. Although the polyp size was <1 cm in 85% of the cohort, a significant number of participants harbored advanced lesions. A disturbing incidence of lesions in women 30-49 years was located mainly in the left colon. One-third of the important pathology resides exclusively in the right colon. ROC curves demonstrated that with the current starting age of screening at 50 years, 92% of polyps and 95% of adenomas could be detected by colonoscopy, but a number of potential precancerous lesions will appear at an earlier age and therefore will be missed. The present study supported the notion that it is critical to reduce screening initiation below the currently accepted age of 50 years. Colonoscopy is a suitable method for addressing the increased prevalence of proximal lesions and the meticulous resection of smaller polyps.

Enzymes of Fibrosis in Chronic Liver Disease.

Introduction: Liver fibrosis has been extensively studied at the cellular and molecular level, but very few data exist on the final enzymatic stages of collagen synthesis (prolyl hydroxylase, PH) and degradation (matrix metalloproteinases, MMPs), particularly in primary biliary cholangitis (PBC). Aim: We studied enzyme activities in liver tissue from patients with chronic liver diseases and compared them to normal livers. Patients: Eighteen patients with PBC of early and late stages (Ludwig's classification) and seven on treatment with ursodeoxycholate (UDCA) were studied and compared to 34 patients with alcoholic liver disease (ALD), 25 patients with chronic viral liver disease and five normal biopsies. Sera were available from a total of 140 patients. Methods: The tritiated water released from the tritiated proline was measured in PH assessment. 14C intact and heat-denatured collagen substrates were used to measure collagenase and gelatinases, respectively. 3H Elastin was the substrate for elastase. In serum, ELISAs were used for MMP-1, TIMP-1, and TIMP-2 measurements while MMP-2 and MMP-9 were estimated by zymography. Results: PH was significantly increased in early and late PBC. Collagenase was reduced only in the late stages (p < 0.01), where the ratio PH/collagenase was increased. UDCA treatment restored values to almost normal. Gelatinases were reduced in late stages (p < 0.05). In contrast to PBC and ALD fibrosis, collagen synthesis is not increased in viral fibrosis. The balance shifted towards collagen deposition due to reduced degradation. Interestingly, gelatinolytic activity is not impaired in ALD. Elastase was similar to controls in all diseases studied. TIMP-1 was reduced in early PBC and viral and alcoholic hepatitis and cirrhosis (p < 0.001). Conclusions: (1) There is evidence that collagen synthesis increases in the early stages of PBC, but the collagenolytic mechanism may compensate for the increased synthesis. (2) In viral disease, fibrosis may be due to decreased degradation rather than increased synthesis. (3) The final biochemical stages of liver fibrosis may be quantitatively different according to underlying etiology.

Nutritional Assessment of Greek Liver Cirrhosis Patients: Mini Nutritional Assessment Predicts Mortality.

Malnutrition is highly prevalent in liver cirrhosis (LC). It increases as the severity of the disease progresses and it is related to poor survival. The objectives of the study were the nutritional assessment of Greek LC patients, using various nutritional assessment and screening tools, and the comparison of their predictive value for mortality. In total, 137 (77 male) consecutive LC patients (median age: 67 years) were assessed with subjective global assessment (SGA) and mini nutritional assessment (MNA) questionnaires, anthropometrics, handgrip strength (HGS) tests, and bioelectric impedance analysis (BIA), in comparison to a control group of 148 healthy people. Disease severity was assessed using the model for end-stage liver disease (MELD) scores. Patients were followed up for a median of 19 months. Survival curves were calculated using the Kaplan-Meier method. In total, 60% and 43% of patients were of adequate nutritional status by SGA and MNA, respectively, which was confirmed by most anthropometric measurements. MNA and SGA scores correlated significantly with anthropometrics and BIA-derived parameters. Besides the MELD score, mid-arm circumference (MAC), triceps skinfold (TSF), BIA's phase angle (Pha), and MNA predicted mortality in cirrhotic patients. The nutritional assessment demonstrated an unexpectedly high prevalence of well-nourished LC patients. MNA was a strong predictor of mortality.

Spontaneous bacterial peritonitis: a prospective Greek multicenter study of its epidemiology, microbiology, and outcomes.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is an ominous complication of decompensated cirrhosis. This study aimed to assess several epidemiological, clinical, microbiological and outcome characteristics in Greek patients with SBP, as no solid representative nationwide data of this type was available. METHODS: During a 3-year period, 77 consecutive patients with SBP (61 male; median age: 67 years; model for end-stage liver disease [MELD] score: 20), diagnosed and followed in 5 tertiary liver units, were prospectively recruited and studied. Various prognostic factors for disease outcome were studied. RESULTS: Thirty-eight patients had alcohol-related cirrhosis, 17 viral hepatitis, 6 non-alcoholic steatohepatitis, 6 autoimmune liver diseases, and 10 cryptogenic cirrhosis. Hepatocellular carcinoma (HCC) was present in 23 (29.9%), whereas 10 (13%) had portal vein thrombosis. The first SBP episode at baseline was community-acquired in 53 (68.8%), while in 24 (31.1%) was hospital-acquired, with predominant symptoms abdominal pain and encephalopathy. A positive ascitic culture was documented in 36% of patients in the initial episode, with almost equal gram (+) and gram (-) pathogens, including 3 multidrug-resistant pathogens. Significant factors for 6-month survival were: higher MELD score, previous b-blocker use, lower serum albumin, higher lactate on admission and need for vasopressors, while factors for 12-month survival were MELD score and lactate. For overall survival, higher MELD score and lactate along with HCC presence were negative predictive factors. CONCLUSIONS: MELD score, lactate, albumin, HCC and treatment with vasopressors were predictive of survival in SBP patients. In hospital-acquired SBP the prevalence of difficult-to-treat pathogens was higher.

TNF receptors in Kupffer cells.

INTRODUCTION: Somatostatin is a mediator of immune functions and has been used as an antineoplastic agent in animal models and human neoplasias. We have demonstrated that Octreotide inhibits only LPS induced secretion of proinflammatory cytokines including TNFa by Kupffer cells (KC). We, therefore, tested the hypothesis that somatostatin modulates the expression of tumor necrosis factor alpha (TNF?) receptors and apoptosis of KC. METHODS: Rat KC were isolated by centrifugal elutriation. TNFR1 and TNFR2 expression was studied by RT-PCR, quantitative PCR, Western Blot and immunofluorescence before and after Octreotide pre-incubation. Apoptosis was assessed by quantitative measurement of cytoplasmic histone-associated DNA fragments. TNFa mRNA expression was assessed by semiquantitative PCR and TNFa was measured in cell supernatants by ELISA. RESULTS: TNFR1 and TNFR2 mRNA are constitutively expressed in KC. Octreotide incubation increased both receptors expression with a peak at 6?h and return to basal levels at 24?h. TNFR1 was mostly influenced. However, only increase in TNFR2 protein was identified, whereas a band at 90 kD was present instead of a band at 55 kD as expected for TNFR1. TNF? mRNA expression was inhibited by Octreotide and a significant inhibition was observed at 48?h. TNF had no effect on KC apoptosis, whereas Octreotide significantly increased their apoptosis, and this effect was not influenced by co-incubation with TNFa. CONCLUSION: TNFR1 and TNFR2 are constitutively expressed in KC and their expression is strongly increased by somatostatin. Moreover, somatostatin increases KC apoptosis. These findings may in part explain the antineoplasmatic effect of somatostatin.

Role of ghrelin and insulin-like growth factor binding protein-3 in the development of osteoporosis in inflammatory bowel disease.

BACKGROUND: A high prevalence of bone loss is observed in patients with inflammatory bowel disease (IBD). Leptin, ghrelin, insulin-like growth factor (IGF)-1, and IGF binding protein (IGFBP)-3 have been suggested to interfere in the bone metabolism. The aim of this study was to investigate the role of these peptides in the development of osteoporosis in IBD. METHODS: One hundred and eighteen consecutive IBD patients were included. All patients underwent bone densitometry by dual energy x-ray absorptiometry at the femoral neck and lumbar spine levels. Serum samples were collected from all patients and analyzed for concentrations of the aforementioned peptides by radioimmunoassay. RESULTS: Forty (33.9%) patients were normal, 55 (46.6%) were osteopenic, and 23 (19.5%) were osteoporotic. Positive statistically significant correlations were found between body mass index (BMI), leptin, IGFBP-3 levels, and the bone mineral density (BMD) of the femoral neck and lumbar spine. Moreover, an inverse statistically significant correlation was found between BMD of the femoral neck and the lumbar spine, and age, duration of the disease, and ghrelin levels. Multivariate analysis revealed that the most significant factors associated with the BMD were age and BMI. A weak but statistically significant correlation was found between IGFBP-3 and femoral neck BMD (P=0.045) and between ghrelin and spine BMD (P=0.039). No correlation was observed between leptin and BMD. CONCLUSIONS: Low BMI is the most important independent risk factor for osteoporosis in IBD patients. There is no independent influence of leptin but ghrelin and IGFBP-3 may play a role in the bone metabolism in the IBD.

Upper gastrointestinal endoscopy for dyspepsia: exploratory study of factors influencing patient compliance in Greece.

BACKGROUND: Upper gastrointestinal endoscopy is the most preferable diagnostic examination for patients over fifty when upper gastrointestinal symptoms appear. However, limited knowledge exists in concerns to the compliance of primary care patients' to the doctors' recommendations for endoscopy. METHODS: Patients who visited primary care practices in Greece and experienced upper gastrointestinal symptoms within a 10 days screening study, were referred for an upper endoscopy exam. The patients which refused to complete the endoscopy exam, were interviewed by the use of an open- ended translated and validated questionnaire, the Identification of Dyspepsia in General Population (IDGP) questionnaire. A qualitative thematic analysis grounded on the theory of planned behavior was performed to reveal the reasons for patients' refusal, while socio-demographic predictors were also assessed. RESULTS: Nine hundred and ninety two patients were recorded, 159 of them (16%) were found positive for dyspepsia and gastro-esophageal reflux disease according to the IDGP questionnaire. Out of the above, 131 (83.6%) patients refused further investigation with endoscopy. Patients who refused upper endoscopy were predominantly female (87.8%) (p = 0.036) and over the age of 50. The lack of severe symptoms, fear of pain, concerns of sedation, comorbidity and competing life demands were reported by patients as barriers to performing an endoscopic investigation. CONCLUSIONS: Patients with dyspepsia in rural Greece tend to avoid upper gastrointestinal endoscopy, with two major axons considered to be the causes of patients' refusal: their beliefs towards endoscopy and their personal capability to cope with it. Future research examining reasons of low compliance should be carried out in combination with modern behavioral theories so as to investigate into the above.

Antiglycan antibodies in Greek patients with inflammatory bowel disease.

BACKGROUND: Antiglycan antibodies have recently been reported to be associated with Crohn's disease (CD). These antibodies include anti-Saccharomyces cerevisiae mannan antibodies (ASCA), anti-laminariobioside carbohydrate antibodies (ALCA), anti-chitobioside carbohydrate antibodies (ACCA), and anti-mannobioside carbohydrate antibodies (AMCA). AIMS: The aim of this study was to evaluate their diagnostic accuracy in Greek patients with inflammatory bowel disease (IBD). METHODS: Serum was collected from 191 patients with IBD (85 with ulcerative colitis (UC) and 106 with CD), 29 cases with other causes of intestinal inflammation and 96 healthy controls. Antiglycan antibodies were measured using commercially available enzyme immunoassays. RESULTS: Higher levels of antiglycan antibodies were detected in patients with CD compared to patients with UC and controls. Although all types of antiglycan antibodies had a high specificity for diagnosing CD, their sensitivity was rather low, with best results obtained with ASCA and ALCA (41.5 and 52.8%, respectively). Increased levels of ASCA and ALCA were associated with stricturing and penetrating disease phenotype, and the need for surgery (p < 0.05). CONCLUSIONS: Antiglycan antibodies in Greek IBD patients are significantly associated with CD, and especially to phenotypes of complicated disease, with ASCA and ALCA exhibiting the highest sensitivity.