Mairi Koulentaki

Epstein Barr Virus hepatitis

OBJECTIVES Epstein-Barr Virus (EBV) infection has the potential to establish life-long, benign infections in their hosts. Although biochemical evidence of hepatocellular damage is common, jaundice is uncommon and complete recovery is the rule. The present study describes clinical characteristics and changes of liver function tests during the course of infectious mononucleosis. PATIENTS AND METHODS All immunocompetent patients with hepatic dysfunction associated with acute EBV infection, cared for at the University Hospital of Heraklion, over a 6-year period, were identified and retrospectively studied. RESULTS The study included 41 patients with a median age of 18.5 (15-51) years. Aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) were increased in an average maximum of 5-fold. Both transaminase levels started to rise 2 days after the clinical onset of the disease, and returned to normal after a period of 20 days. Alkaline-phosphatase (ALP), γ-glutamyltransferase (γ-GT) and bilirubin levels also increased above the normal values during the course of the disease and returned to normal after a period of 20, 30 and 22 days respectively. The changes of mean AST and ALT levels over time were statistically significant, while those of mean ALP, γ-GT and bilirubin levels over time were not. Anicteric cholestatic liver disease was observed in 24 patients (59%), while icteric only in 2 (6%). CONCLUSION Liver involvement in acute EBV infection represents mild and self-limited hepatitis with predominantly cholestatic features.

Primary Biliary Cirrhosis in a genetically homogeneous population: Disease associations and familial occurrence rates

BackgroundPrimary 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.Methods111 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.ResultsDyslipidaemia 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%.ConclusionsDyslipidaemia 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.

Geoepidemiology and space–time analysis of Primary biliary cirrhosis in Crete, Greece

The prevalence of Primary biliary cirrhosis varies in different geographical areas. This might reflect genetic or environmental risk factors. We aimed to define Primary biliary cirrhosis prevalence and incidence, describe patients spatial distribution, generate prediction maps and detect any possible routing pattern of time‐spatial appearance of the disease in Crete, Greece.

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

Eur J Clin Invest 2012

Clinical outcomes of compensated and decompensated cirrhosis: A long term study

AIM To study these characteristics and prognostic patterns in a Greek patient population. METHODS We analyzed a large cohort of cirrhotic patients referred to the department of Gastroenterology and Hepatology and the outpatient clinics of this tertiary hospital, between 1991 and 2008. We included patients with established cirrhosis, either compensated or decompensated, and further decompensation episodes were registered. A data base was maintained and updated prospectively throughout the study period. We analyzed differences in cirrhosis aetiology, time to and mode of decompensation, hepatocellular carcinoma (HCC) occurrence and ultimately patient survival. RESULTS Five hundreds and twenty-two patients with median age 67 (range, 29-91) years and average follow up 9 years-10 mo (range, 1-206 mo) were studied. Commonest aetiology was hepatitis C virus (HCV, 41%) followed by alcohol (31%). The median survival time in compensated cirrhotics was 115 mo (95%CI: 95-133), whereas in decompensated patients was 55 mo (95%CI: 36-75). HCV patients survived longer while HBV patients had over twice the risk of death of HCV patients. The median time to decompensation was 65 mo (95%CI: 51-79), with alcoholics having the highest risk (RR = 2.1 vs HCV patients). Hepatitis B virus (HBV) patients had the highest risk of HCC, alcoholics the lowest. Leading causes of death: liver failure, hepatorenal syndrome, sepsis and HCC progression. CONCLUSION Cirrhosis aetiology and decompensation at presentation were predictors of survival. Alcoholics had the highest decompensation risk, HBV cirrhotics the highest risk of HCC and HCV cirrhotics the highest decompensation-free time.

Serum surrogate markers of liver fibrosis in primary biliary cirrhosis

BACKGROUND Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease. METHODS Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed. RESULTS All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p<0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers. CONCLUSION No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC.

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

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.

Long-term change in incidence and risk factors of cirrhosis and hepatocellular carcinoma in Crete, Greece: a 25-year study

Background No sequential long-term data exist for Greece on the etiological evolution and incidence of cirrhosis and hepatocellular carcinoma. Therefore, we studied their etiological evolution over a period of 25 years in the island of Crete. Methods We studied 812 cases of cirrhosis (561 male, median age 69 years) and 321 cases of hepatocellular carcinoma (234 male, median age 70 years) from the database of our Center. Cases were classified into five-year periods according to incidence and etiology (hepatitis B, hepatitis C, alcohol, alcohol plus viral, and non-alcoholic fatty liver disease). Results Overall, there was an increase in the incidence of hepatocellular carcinoma. A significant fourfold reduction in the incidence of hepatitis C-related cirrhosis was observed, which was degraded from first to third place as a risk factor for cirrhosis. Alcohol gradually became the first risk factor in cirrhosis (1990-94: 36.1%, 2010-14: 52.3%) and carcinoma, while the steepest increase in incidence of cirrhosis and carcinoma was associated with non-alcoholic fatty liver disease. Conclusions The incidence of cirrhosis remained constant over the years, but the incidence of hepatocellular carcinoma increased during the last decade. Risk factors for cirrhosis and hepatocellular carcinoma have changed over the past 25 years in Crete. The initial high hepatitis C virus association has significantly decreased, with alcohol now ranking first among risk factors. Non-alcoholic fatty liver disease is continually increasing and is a prominent risk factor for cirrhosis and hepatocellular carcinoma.

GABA A receptor polymorphisms in alcohol use disorder in the GWAS era

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. GABAA 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 GABAA receptors, with all the reported SNPs, are presented. Genetic studies and meta-analyses examining polymorphisms of the GABAA 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 GABAA receptors and AUD. Restrictions and perspectives of the different findings are discussed.

PTH-107 Geoepidemiology of hepatocellular carcinoma (hcc) in the island of crete. a possible role of pesticides

Introduction Geoepidemiological data of HCC are lacking in Greece. The island of Crete has a genetically homogeneous population with minimal immigration and therefore is suitable for such studies attempting to identify a possible contribution of environmental factors in HCC. Method We used a data base of HCC patients constructed over the past 20 years in our Unit, the reference centre for liver disease in the island. Similar data bases for chronic HCV and HBV were also used. All patients had a histological confirmation of diagnosis. Recorded data included gender, date and place of birth and place of residence for the last 15 years. The geographic area of the study comprised the four prefectures of the island of Crete. Population statistics from 1980–2010 were obtained from the Hellenic Statistical Authority. 316 HCC patients, 633 HCV and 392 HBV patients were included in the study. Time-spatial methods were applied in Gis – ArcMap 10 software. A spatial statistical test that measures spatial autocorrelation (Moran`s index) was applied at a confidence level of 95%, in order to detect any possible significant difference between the spatial distribution to place of residence. Density maps with the spatial clusters configuring the prevalence of the disease of all provinces in the island were created. Kriging Interpolation method was applied, to produce a prediction map of HCC in Crete. Results HCV is present in pockets of high prevalence while HBV is more uniformly distributed. HCC is more prevalent in Eastern Crete. A significant spatial autocorrelation between HCC and either HCV (Moran’ I=0.64, p < 0.001) or HBV (Moran’ I=0.74, p < 0.001) was found as expected. However there is a discrepancy in the South East of Crete, where a higher prevalence of HCC than expected from the dispersion of HCV and HBV was observed. Prediction maps also identified this area as the main source of future HCC cases. This is an area where extensive use of pesticides in large green houses is widely practiced. Conclusion 1) HCC is mostly found in Eastern Crete and is broadly associated with the dispersion of chronic HCV and more so with Chronic HBV. 2) In an area with widespread use of pesticides a higher than expected spatial distribution of HCC was detected. Disclosure of interest None Declared.