Purpose: To study the production of angiodrastic chemokines by colonic cancer cell lines. Methods: A pro-angiogenic factor (VEGF), two angiogenic chemokines (CXCL8, CXCL6), and one angiostatic (CXCL4) chemokine were measured by ELISA in... more
Purpose: To study the production of angiodrastic chemokines by colonic cancer cell lines. Methods: A pro-angiogenic factor (VEGF), two angiogenic chemokines (CXCL8, CXCL6), and one angiostatic (CXCL4) chemokine were measured by ELISA in the supernatants of the colon cancer cell lines HT-29 and Caco-2. Cells were cultured for 24 h in the presence of serum from cancer patients or healthy individuals. Results were analyzed by one-way ANOVA and the General Linear Model for repeated measures. Results: Colonic epithelial cells are potent producers of angiodrastic chemokines. HT-29 and Caco-2 cells produce all four chemokines under basal conditions and 24 h after incubation with human serum. The secretion response, however, was completely different. HT-29 cells produce more CXCL8 and VEGF irrespective of culture conditions, while Caco-2 cells seem unresponsive with respect to CXCL6 and CXCL4. Moreover, HT-29 cells produce more CXCL8 and VEGF when incubated with cancer serum, contrary to Ca...
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Background: The aim of our study was to evaluate the safety and efficacy of triple therapy using boceprevir (BOC) with pegylated interferon (pIFN)/ribavirin (RBV) in chronic hepatitis C (CHC) genotype 1 (G1) treatment-experienced patients... more
Background: The aim of our study was to evaluate the safety and efficacy of triple therapy using boceprevir (BOC) with pegylated interferon (pIFN)/ribavirin (RBV) in chronic hepatitis C (CHC) genotype 1 (G1) treatment-experienced patients with advanced fibrosis or compensated cirrhosis. Methods: We report the Greek experience on the first CHC patients who received BOC-based regimen. From September 2011 to June 2012, 26 treatment-experienced CHC patients and G1 with bridging fibrosis or compensated cirrhosis received 48 weeks of BOC+pIFN+RBV antiviral therapy. Data on complete blood counts and HCV RNA levels were obtained prior to therapy, at treatment weeks 4, 8, 12, 24, 36, 48 and 24 weeks after the end of treatment. Results: A full set analysis was performed in 25 of 26 patients. Nine patients (36%) achieved sustained viral response (SVR). Ten patients (40%) stopped the therapy because of futility rules and 3 (12%) due to adverse events. Four patients (16%) developed a virological breakthrough (3 of those presented futility rules as well) and 2 (8%) relapse. All patients who achieved SVR had G 1b, 6 (67%) were non-cirrhotic and 5 (55%) had >1 log decline in baseline HCV RNA levels at week 4 of the treatment. There were no deaths, while two patients were hospitalized due to side effects. Conclusion: The triple therapy with BOC+pIFN+RBV in this cohort of real-life treatment-experienced CHC G1 patients and advanced liver disease was safe offering cure in the majority of those who could tolerate and complete treatment under a close monitoring.
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Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms. Damaged organelles, lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell. Investigations on... more
Autophagy is the liver cell energy recycling system regulating a variety of homeostatic mechanisms. Damaged organelles, lipids and proteins are degraded in the lysosomes and their elements are re-used by the cell. Investigations on autophagy have led to the award of two Nobel Prizes and a health of important reports. In this review we describe the fundamental functions of autophagy in the liver including new data on the regulation of autophagy. Moreover we emphasize the fact that autophagy acts like a two edge sword in many occasions with the most prominent paradigm being its involvement in the initiation and progress of hepatocellular carcinoma. We also focused to the implication of autophagy and its specialized forms of lipophagy and mitophagy in the pathogenesis of various liver diseases. We analyzed autophagy not only in well studied diseases, like alcoholic and nonalcoholic fatty liver and liver fibrosis but also in viral hepatitis, biliary diseases, autoimmune hepatitis and rare diseases including inherited metabolic diseases and also acetaminophene hepatotoxicity. We also stressed the different consequences that activation or impairment of autophagy may have in hepatocytes as opposed to Kupffer cells, sinusoidal endothelial cells or hepatic stellate cells. Finally, we analyzed the limited clinical data compared to the extensive experimental evidence and the possible future therapeutic interventions based on autophagy manipulation.
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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... more
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.
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Research Interests: Immunology, Protein, Medicine, Saccharomyces cerevisiae, Inflammatory Bowel Disease, and 12 moreUlcerative colitis, Crete, Expression, Differential Diagnosis, Clinical Sciences, GASTROENTEROLOGY AND HEPATOLOGY., Prevalence, Antibody, Crohns Disease, Positive predictive value, small bowel, and Negative predictive value
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Introduction Lamivudine has been largely replaced for the treatment of chronic HBV infection by new (and more expensive) antivirals with a high viral resistance barrier. It has been reported that lamivudine resistance can be as high as... more
Introduction Lamivudine has been largely replaced for the treatment of chronic HBV infection by new (and more expensive) antivirals with a high viral resistance barrier. It has been reported that lamivudine resistance can be as high as 20% after one year and up to 80% at five years. We therefore assessed a cohort of our patients for the development of Lamivudine resistance over time. Method 100 chronic HBV hepatitis patients, histologically diagnosed (male 67, female 33), median age 59 years (range 20–75), initially received lamivudine and were followed up for at least 5 years. All were HBeAg negative, HbeAb positive. Genotype D was found in all 23 patients genotyped. All were non-cirrhotic on liver biopsy before treatment (66% Ishak fibrosis stage 2–3, 34% Ishak stage 4–5). Median HBV DNA at the commencement of treatment was 450000 IU/ml. Only 12 patients had a viral load over 1000000 IU/ml. Lamivudine resistance was considered when an increase of 2 logs in the viral load, followed by an aminotransferase increase after an initial response was noted on follow up. Results All patients responded to lamivudine with normalisation of aminotransferases and subsequent reduction of HBV DNA to less than 100 IU/ml within 6 months from treatment initiation. Lamivudine resistance was 5% at one year, 10% at 2 years, 17% at 4 years and 21% at 5 years Conclusion The risk for lamivudine resistance development in our chronic HBV hepatitis patients is well below the reported in the literature. Whether this is due to the relative lower levels of viral load or to the lack of cirrhotics in our cohort remains to be further examined. Nonetheless we believe that in view of the low cost, lamivudine use should possibly be reconsidered as a first line treatment In HBV infection for non-cirrhotic patients with a viral DNA below 1000000 IU/ml. Disclosure of interest None Declared.
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A case of a “difficult to treat” patient with chronic hepatitis C is presented, who experienced multiple problems, leading to significant drug reductions or discontinuations. Nevertheless, after an initial response, ribavirin monotherapy... more
A case of a “difficult to treat” patient with chronic hepatitis C is presented, who experienced multiple problems, leading to significant drug reductions or discontinuations. Nevertheless, after an initial response, ribavirin monotherapy for a significant period proved be an important factor in achieving sustained virological response.
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To evaluate the efficacy of gemcitabine as palliative treatment in patients with advanced pancreatic cancer (PC) previously treated with placement of a covered metal biliary stent, taking into account survival and quality of life (QoL).... more
To evaluate the efficacy of gemcitabine as palliative treatment in patients with advanced pancreatic cancer (PC) previously treated with placement of a covered metal biliary stent, taking into account survival and quality of life (QoL). Forty-nine patients with unresectable PC and obstructive jaundice, previously treated with the placement of a covered metal biliary endoprosthesis, were randomized to receive gemcitabine (group A: 9 males, 7 females) or to be followed without any anticancer intervention (group B: 18 males, 15 females). Gemcitabine was administered weekly as intravenous (i.v.) 30 min infusion of 1000 mg/m2 for 3 consecutive weeks followed by 1-week rest (28-day cycle). QoL was evaluated with the QLQ-C30 questionnaire. 229 gemcitabine doses were administered (median doses per patient 14.3, range 7-22). No statistically significant differences were observed regarding survival (group A: median 21 weeks, range 13-33; group B: median 22 weeks, range 13-29; p=0.809). Accord...
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Research Interests: Gastroenterology, Greece, Humans, Internal Medicine, Liver Cirrhosis, and 15 moreFemale, Hepatocellular Carcinoma, Globulin, Clinical Sciences, Aged, Adult, Adrenal cortex, Biological markers, Chi Square Distribution, Cirrhosis, Area Under Curve, Liver function tests, Acute Disease, hydrocortisone, and Esophageal and gastric varices
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Research Interests: Gastroenterology, Medicine, Fibrinogen, Inflammatory Bowel Disease, Humans, and 15 moreInternal Medicine, Genetic Testing, Female, Male, Clinical Sciences, Middle Aged, Adult, Disease Activity, Antithrombin, Crohn Disease, Inflammatory Bowel Diseases, Lupus Anticoagulant, Activity index, Factor V Leiden, and protein S
Research Interests: Autoimmune Disease, Autoimmune diseases, Celiac Disease, Chronic Disease, Alkaline phosphatase, and 15 moreEnzyme, Clinical Sciences, Aged, Antibody, Adult, Cirrhosis, Asymptomatic, Coeliac Disease, Chronic Liver Disease, Autoantibodies, Autoimmune Hepatitis, Cholangitis, cholestasis, BMC, and Blood Donor
Research Interests: Pathology, Gastroenterology, Adolescent, Medicine, Humans, and 15 moreInternal Medicine, Female, Male, Hyperplasia, Clinical Sciences, Aged, Middle Aged, Adult, Malignant Transformation, Adenoma, Neurosciences, The American, Colorectal Neoplasms, Hyperplastic Polyp, and Paediatrics and reproductive medicine
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Objective: To study the incidence of ulcerative colitis and to analyse the pattern of the disease in the prefecture of Heraklion, Crete. Participants: The population at risk comprised 263,670 inhabitants in the prefecture of Heraklion... more
Objective: To study the incidence of ulcerative colitis and to analyse the pattern of the disease in the prefecture of Heraklion, Crete. Participants: The population at risk comprised 263,670 inhabitants in the prefecture of Heraklion (2641 km2). The two regional hospitals, five health centres, 109 private family doctors and 145 specialists participated in the study. Methods: A prospective and population-based epidemiological study of ulcerative colitis over five years from 1990 to the end of 1994. Results: Overall, 117 patients with ulcerative colitis (75 males and 42 females) were newly diagnosed during the study period. The mean annual incidence of the disease for the years 1990-1994 was 8.9 per 10(5) inhabitants (95% CI 7.2-10.4). The male to female ratio was 1.8:1. There were no significant difference between the age-specific incidences of the age groups. The majority (51.3%) of the patients were exsmokers and one-third had never smoked. A family history of first-degree relatives positive for inflammatory bowel disease was obtained in 9.6% of our patients. Conclusion: Ulcerative colitis is common in Crete; its incidence is as high as in Northern Europe.
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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... more
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 subs...
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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... more
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 confirme...
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Using autoimmune antibodies from a patient with primary biliary cirrhosis we have identified a 68 kDa nuclear envelope protein, termed PBC68. This protein is co-precipitated with a 98 kDa and a 250 kDa polypeptide and is distinct from the... more
Using autoimmune antibodies from a patient with primary biliary cirrhosis we have identified a 68 kDa nuclear envelope protein, termed PBC68. This protein is co-precipitated with a 98 kDa and a 250 kDa polypeptide and is distinct from the nuclear lamins. Immunostaining of digitonin-permeabilized cells indicates that PBC68 is restricted to the inner (nucleoplasmic) face of the nuclear envelope, while indirect immunofluorescence and immunoelectron microscopy show that PBC68 is located on fibrillar structures emanating from the nuclear pore complex. The autoantigen is modified at early prophase and disassembles at prometaphase concurrently with the breakdown of the nuclear envelope. The disassembled material, instead of diffusing throughout the cytoplasm as other nucleoporins, is targeted to the mitotic spindle and remains stably bound to it until anaphase. At telophase PBC68 is released from the mitotic apparatus and reassembles late, after incorporation of LAP2B and B-type lamins, on...
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Background The outcome of primary biliary cholangitis (PBC) is affected by both genetic and environmental factors. Objective The aim of this study was to study the effect of smoking on liver histology and mortality in a genetically... more
Background The outcome of primary biliary cholangitis (PBC) is affected by both genetic and environmental factors. Objective The aim of this study was to study the effect of smoking on liver histology and mortality in a genetically homogeneous population having PBC. Patients and methods Smoking and drinking habits at diagnosis (based on standard criteria) were recorded in 171 Cretan patients with PBC (163 women). A total of 148 patients had a liver biopsy. Odds ratios were calculated with logistic regression analysis. Kaplan–Meier curves were used for mortality estimation. Results Smoking was associated with alcohol consumption of more than 20 g/day [adjusted odds ratio (AOR)=2.20, 95% CI: 1.029–4.099], severe steatosis (AOR=5.31, 95% CI: 2.019–9.919), and fibrosis stage F3–F4 (AOR=1.21, 95% CI: 1.015–3.031). Heavy smoking, years of passive smoking, and serious necroinflammatiοn were independent factors associated with advanced fibrosis after adjustment for sex, age, BMI, and alcoho...
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Alcohol use disorder (AUD) is a chronic, relapsing, neuro-psychiatric illness of high prevalence and with a serious public health impact worldwide. It is complex and polygenic, with a heritability of about 50%, and influenced by... more
Alcohol use disorder (AUD) is a chronic, relapsing, neuro-psychiatric illness of high prevalence and with a serious public health impact worldwide. It is complex and polygenic, with a heritability of about 50%, and influenced by environmental causal heterogeneity. Risk factors associated with its etiology have a genetic component. GABA (γ-aminobutyric acid) is a major inhibitory neurotransmitter in mammalian brain. GABA receptors are believed to mediate some of the physiological and behavioral actions of alcohol. In this critical review, relevant genetic terms and type and methodology of the genetic studies are briefly explained. Postulated candidate genes that encode subunits of GABA receptors, with all the reported SNPs, are presented. Genetic studies and meta-analyses examining polymorphisms of the GABA receptor and their association with AUD predisposition are presented. The data are critically examined with reference to recent GWAS studies that failed to show relations between ...
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Background There is evidence that genotyping for the thiopurine S-methyltransferase (TPMT) gene variants is useful for the prediction of response to thiopurine analogs (azathioprine and 6-mercaptopurine) in patients with inflammatory... more
Background There is evidence that genotyping for the thiopurine S-methyltransferase (TPMT) gene variants is useful for the prediction of response to thiopurine analogs (azathioprine and 6-mercaptopurine) in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of TPMT gene polymorphisms in a genetic homogenous population of IBD patients in Crete and to correlate the results with adverse reactions to thiopurine drugs. Patients and methods Genotyping for the most common TPMT variants TPMT*2, TPMT*3A, TPMT3*C, and TPMT*3B was performed using the PCR-restriction fragment length polymorphism method in 223 consecutive IBD patients and 119 age-matched and sex-matched healthy controls. The hospital medical records were reviewed for thiopurine use in these patients and related adverse events. Results The prevalence of TPMT variants TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C was 1.8, 2.7, 1.3, and 1.8%, respectively. The G238C mutation was det...
Research Interests: Adolescent, Medicine, Greece, Inflammatory Bowel Disease, Humans, and 15 moreMutation, Female, Male, Clinical Sciences, Aged, Middle Aged, Genotype, Adult, Genotyping, European Continental Ancestry Group, Azathioprine, Inflammatory Bowel Diseases, Case Control Studies, Immunosuppressive Agents, and leukopenia
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Carcinoma of the ampulla of Vater is an infrequent tumor that can be diagnosed, early. Twenty-four patients with histologically proven carcinoma of the ampulla of Vater were retrospectively studied and their data were analyzed. Most... more
Carcinoma of the ampulla of Vater is an infrequent tumor that can be diagnosed, early. Twenty-four patients with histologically proven carcinoma of the ampulla of Vater were retrospectively studied and their data were analyzed. Most common presenting symptoms were jaundice (67%), weight loss (58%), fever and pain (54%). Endoscopic biopsies which were taken in 19 patients revealed carcinoma or dysplasia in 15 patients and were normal for in the rest. Twelve patients were treated with a Whipple's resection, 5 with local resection, 2 with palliative surgery and 2 received a stent endoscopically. During a mean follow-up period of 25 months, (range 1-82) 12 deaths were noted, and one patient was lost during follow-up. Presenting symptoms, endoscopic and histological findings were similar as in other series. The contribution of duodenoscopy, ERCP and endoscopic biopsy is essential for diagnosis but endoscopic biopsies may be misleading.