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The night eating syndrome (NES) is characterized by excessive food intake during the evening and night hours, with 25% of the daily intake being consumed post-dinner, paired with ep-isodes of nocturnal food intake, at a frequency of more than twice weekly. The NES has been associated with a misaligned circadian rhythm related to a delay in overall food intake, increased energy and fat consumption. The present cross-sectional study aimed to assess NES in a Greek population and evaluate possible links between NES and chronotype. NES was assessed using the Night Eating Questionnaire (NEQ), and circadian rhythm, sleep and mood were evaluated with the Sleep, Circadian Rhythms, and Mood (SCRAM) questionnaire. A total of 533 adults participated in the study. A relatively high prevalence of NES was revealed, with more than 8.1% (NEQ ≥ 30) of the participants reporting experiencing NES symptoms, depending on the NEQ threshold used. Most participants had the intermediate chronotype. NEQ score was positively associated with the morning chronotype, and SCRAM was negatively related to "Good Sleep". Each point increment in the depression score was associated with 6% higher odds of NES. The early identification of NES gains importance in clinical practice, in a collective effort aiming to reduce NES symptomatology and its detrimental health effects.

Background: FibroMeter and FibroMeter vibration-controlled transient elastography (FibroMeter VCTE) were assessed in a Greek cohort of patients with chronic viral hepatitis (CVH) B and C or metabolic dysfunction-associated steatotic liver disease (MASLD) to evaluate their accuracy in predicting advanced liver fibrosis against other well-validated noninvasive markers., Methods: Group 1: n=83 CVH and group 2: n=38 MASLD patients underwent liver biopsy and transient elastography (TE) on the same day as sera collection. FibroMeter scores APRI and FIB-4 were calculated in all 121 patients, while MASLD fibrosis score (MFS) was also calculated in group 2., Results: In CVH, FibroMeter VCTE performed equivalently to TE and better than the other markers in predicting advanced (≥F3) and significant (≥F2) fibrosis (area under the receiver operating characteristic curve [AUC] 0.887, P<0.001 for F3; AUC 0.766 P<0.001 for F2). FibroMeter Virus (cutoff 0.61) had lower sensitivity (20%) but performed equivalently to APRI and FIB-4. In MASLD, all markers but APRI performed equivalently in predicting advanced fibrosis. FibroMeter VCTE >0.2154 had the same sensitivity (100%) and specificity (81%) as TE (cutoff >7.1 kPa). FibroMeter MASLD >0.25 performed equivalently to MFS and FIB4, but with higher specificity (100%). Both FibroMeter and FibroMeter VCTE correlated with liver histology but not with liver enzymes., Conclusions: FibroMeter VCTE predicts accurately advanced fibrosis in CVH and MASLD, irrespectively of transaminase levels. FibroMeter Virus can be applied only as an alternative marker in CVH, while FibroMeter MASLD performs equally to TE and calculated scores (MFS, FIB-4) in predicting advanced fibrosis in MASLD patients., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Background & Aims: Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes., Methods: We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used., Results: There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival ( p  = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p  = 0.02).Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy ( p  = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p  = 0.84)., Conclusions: Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype., Impact and Implications: Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery., Competing Interests: The authors have no relevant disclosures. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background: Primary biliary cholangitis (PBC) has been long associated with impairment of various aspects of health-related quality of life (HRQoL) with substantial differences among populations. This study evaluated for the first-time the HRQoL in Greek PBC patients in conjunction with clinical and laboratory parameters of patients., Methods: We analyzed prospectively collected data regarding the HRQoL by using the PBC-40 and SF-36 questionnaires in 374 Greek PBC patients and 131 age- and sex-matched non-PBC controls., Results: The PBC-40 questionnaire is a reliable tool for HRQoL assessment in Greek PBC patients (Cronbach's α > 0.7 for all domains). Implementation of PBC-40 and SF-36 demonstrated significant impairment of HRQoL in Greek PBC patients compared to controls ( P < 0.001 for all comparisons). Emotional dysfunction, social impairment, and fatigue (100%, 80.5% and 78%, respectively) were amongst those with the highest, while cognitive dysfunction (32%) with the least impact on quality of life. Fatigue was associated with female sex ( P = 0.02), longer disease duration ( P = 0.01), presence of cirrhosis ( P = 0.02) and positivity for PBC-specific ANA ( P < 0.05), while social dysfunction with increased age ( P < 0.001), longer disease duration ( P < 0.001) and presence of cirrhosis ( P = 0.004). Living in urban areas was linked to impaired social function ( P = 0.04), cognition ( P = 0.02), fatigue ( P = 0.04) and increased total PBC-40 score ( P = 0.01)., Conclusions: Implementation of PBC-40 and SF-36 revealed impaired HRQoL in Greek PBC patients with fatigue, social and emotional dysfunction exerting the highest impact. However, total, and individual PBC-40 scores were lower than that reported in studies from Northern/Central Europe and Canada. Deranged HRQoL was associated with severity of liver disease and presence of PBC-specific ANA., Competing Interests: Conflicts of Interest Dalekos GN is the Editor Board Member of the journal. The article was subject to the journal’s standard procedures, with peer review handled independently of this editor and his research groups., (© 2023 Eirini I. Rigopoulou, Marianna Bakarozi, Ioannis Dimas, Konstantinos Galanis, Vasiliki Lygoura, Nikolaos K. Gatselis, Mairi Koulentaki, George N. Dalekos, published by De Gruyter on behalf of Scholar Media Publishing.)

Autoimmune rheumatic diseases (AIRDs) constitute a set of connective tissue disorders and dysfunctions with akin clinical manifestations and autoantibody responses. AIRD treatment is based on a comprehensive approach, with the primary aim being achieving and attaining disease remission, through the control of inflammation. AIRD therapies have a low target specificity, and this usually propels metabolic disturbances, dyslipidemias and increased cardiovascular risk. Ceramides are implicated in inflammation through several different pathways, many of which sometimes intersect. They serve as signaling molecules for apoptosis, altering immune response and driving endothelial dysfunction and as regulators in the production of other molecules, including sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P). With lipid metabolism being severely altered in AIRD pathology, several studies show that the concentration and variety of ceramides in human tissues is altered in patients with rheumatic diseases compared to controls. As a result, many in vitro and some in vivo (animal) studies research the potential use of ceramides as therapeutic targets in rheumatoid arthritis (RA), ankylosing spondylitis, systemic lupus erythematosus, fibromyalgia syndrome, primary Sjögren's syndrome, systemic sclerosis, myositis, systemic vasculitis and psoriatic arthritis. Furthermore, the majority of ceramide synthesis is diet-centric and, as a result, dietary interventions may alter ceramide concentrations in the blood and affect health. Subsequently, more recently several clinical trials evaluated the possibility of distinct dietary patterns and nutrients to act as anti-ceramide regimes in humans. With nutrition being an important component of AIRD-related complications, the present review details the evidence regarding ceramide levels in patients with AIRDs, the results of anti-ceramide treatments and discusses the possibility of using medical nutritional therapy as a complementary anti-ceramide treatment in rheumatic disease.

Background & Aims: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival., Methods: We collected retrospective data from 2975 PSC patients from 27 centres. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from 1 January 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality., Results: A broad variety of different follow-up strategies were reported. All except one centre used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centres used scheduled endoscopic retrograde cholangiopancreatography (ERCP) in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, was 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years of follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed., Conclusions: Follow-up strategies vary considerably across centres. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumour detection and increased endoscopic treatment of asymptomatic benign biliary strictures., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

HBV RNA is considered as a promising predictor in patients who discontinue nucleos(t)ide analogues (NAs). We determined HBV RNA levels in non-cirrhotic HBeAg-negative patients who discontinued NAs and assessed their predictability for 12-month outcomes. Fifty-seven patients of DARING-B study were included. HBV RNA levels were determined in stored monthly serum samples drawn at 0-3 months after end of therapy (EOT). Other markers previously determined in the same cohort including hepatitis B core-related antigen (HBcrAg) were also assessed. HBV RNA at EOT was detectable in 7% of patients, who developed virological/clinical relapse and required retreatment at month 2; in patients with undetectable EOT HBV RNA, 12-month cumulative rates of virological relapse, clinical relapse and retreatment were 68%, 28% and 21%, respectively (p ≤ 0.008). HBV RNA at month-1 after EOT was detectable in 19% of patients being associated with higher probability only of virological relapse (p = 0.001). HBV RNA levels correlated significantly to HBV DNA, HBcrAg, ALT and interferon-induced protein-10, but not HBsAg levels. Combined EOT HBV RNA and HBcrAg detection and/or HBsAg >1000 IU/ml was associated only with higher probability of retreatment having higher sensitivity and lower specificity than HBV RNA alone. In conclusion, serum HBV RNA is detectable in a minority of non-cirrhotic HBeAg-negative patients under effective long-term NAs therapy offering low sensitivity but 100% specificity for early retreatment due to severe clinical relapses after NA discontinuation. The combinations of EOT HBV RNA with HBcrAg and/or high HBsAg levels increase sensitivity but decrease specificity for prediction of retreatment after NAs withdrawal., (© 2022 John Wiley & Sons Ltd.)

Background & Aims: We have shown previously that mycophenolate mofetil (MMF) might be used as first-line treatment instead of azathioprine (AZA) in individuals with autoimmune hepatitis (AIH). Herein, we present our long-term prospective data on response and outcome after first-line therapy with MMF in treatment-naïve individuals with AIH, as similar data are missing., Methods: During the 21 years of the study, 292 individuals with AIH were included (females: 213; median age: 59 [17-85] years). Patients received either prednisolone 0.5-1 mg/kg/day alone (n = 19) or in combination with AZA 1-2 mg/kg/day (n = 64) or MMF (n = 183). The tapering schedule of prednisolone was identical between groups. We assessed the rates of complete biochemical response (CBR) at 6 months, 12 months, and the end of follow-up; non-response (4 weeks of treatment); CBR off prednisolone; adverse effects; CBR off treatment; histological remission; and overall and liver-related mortality between the AZA and MMF groups., Results: The MMF group had lower non-response ( p  = 0.02) and higher CBR rates at 12 months (86 vs . 71.8%; p <0.05) and the end of follow-up (96 vs . 87.2%; p  = 0.03) than the AZA group. Treatment change was more frequent in the AZA group (43.7 vs . 11%; p <0.001), mostly because of intolerance, whereas MMF was proven safe (serious complications 3.8 vs . 18.8%; p  = 0.0003). MMF-treated patients were more frequently eligible to stop immunosuppression according to the guidelines ( p <0.05). Cirrhosis at diagnosis, age at diagnosis >60 years, and longer disease duration were independent predictors of liver-related mortality., Conclusions: MMF seems an efficient alternative first-line treatment option for AIH, bearing lower non-response at 4 weeks and higher CBR rates at 12 months and the end of follow-up than AZA. In addition, MMF was proven to be safe, leading more frequently to the eligibility for stopping immunosuppression according to the guidelines., Impact and Implications: For more than 40 years, azathioprine (AZA) has been considered the standard treatment for induction and maintenance of response in autoimmune hepatitis (AIH). However, treatment usually needs to be maintained for life, as relapses are common after AZA cessation. Therefore, alternative treatment options are needed. Herein, we showed that the use of mycophenolate mofetil (MMF) as an alternative first-line immunosuppressant was much more efficient in the long-term than AZA as attested by the lower non-response rates at 4 weeks and higher response rates at 12 months and the end of follow-up. Moreover, AZA-treated patients were more prone to change treatment because of intolerance, whereas MMF-treated patients were more often eligible to achieve treatment withdrawal., Competing Interests: The authors have nothing to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Authors.)

Background/aims: As previous real-world studies and meta-analyses have shown that mycophenolate mofetil (MMF) might have better efficacy than azathioprine (AZA) in autoimmune hepatitis (AIH), we conducted a propensity matching study to assess the efficacy and safety of MMF vs. AZA., Methods: All 126 consecutive treatment-naive adult AIH patients, diagnosed and followed in our department since 2016, were included. Patients received prednisolone 0.5-1 mg/kg/day plus either AZA 1-2 mg/kg/day or 1.5-2 g/day MMF. The tapering of prednisolone was identical between groups., Results: After propensity matching score and adjustment for known factors affecting response to treatment and outcome, 64 patients were included in the study (MMF = 32 and AZA = 32). Rates of non-response, complete biochemical response (CBR) at 6 and 12 months, and prednisolone withdrawal (6 months, 12 months, and end of follow-up) were identical between groups. However, MMF treatment was significantly associated with CBR at the end of follow-up [odds ratio (OR) 11.259; 95% CI: 1.3-97.4, p = 0.028]. AZA patients were more prone to stop treatment due to AZA intolerance/insufficient response (p = 0.0001). At the end of follow-up, the overall efficacy of each schedule was also significantly higher in the MMF group compared to the AZA group (p = 0.0001)., Conclusion: We showed for the first time in a propensity matching study that MMF can be used as first-line therapy in AIH as attested by the significantly higher CBR at end of follow-up compared to AZA. Whether this better efficacy is also associated with higher histological remission rates and sustained CBR off immunosuppression needs further evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dalekos, Arvaniti, Gatselis, Samakidou, Gabeta, Rigopoulou, Koukoulis and Zachou.)

Reliable predictors of outcomes after treatment discontinuation in HBeAg-negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon-inducible protein-10 (IP10) and hepatitis B core-related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg-negative CHB patients who discontinued long-term antiviral therapy. All HBsAg-positive (n = 57) patients of the prospective DARING-B study were included and followed monthly for 3 months, every 2/3 months until month-12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE-B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18-month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month-1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100-1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month-1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE-B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg-negative CHB., (© 2019 John Wiley & Sons Ltd.)

Background & Objectives: In the past, patients with haemoglobinopathies were at high risk of acquiring hepatitis C virus (HCV) due to multiple transfusions before HCV screening. In these patients, the coexistence of haemochromatosis and chronic hepatitis C (CHC) often leads to more severe liver disease. We assessed the HCV prevalence, clinical characteristics and outcome in this setting with particular attention to the response to treatment including therapies with the new direct acting antivirals (DAAs)., Methods: The medical records of 81 consecutive patients followed the last 15 years were reviewed retrospectively., Results: 43/81 (53%) patients were anti-HCV positive including 31/43 (72.1%) with CHC (HCV-RNA positive; age 25±7 years; 45.2% with genotype 1b; 19.4% cirrhotics; baseline ferritin 887 ng/ml; range: 81-10.820). Thirty patients received IFN-based therapy with or without ribavirin with sustained virological response (SVR) in 14/30 (46.7%). Eleven patients (9 non-responders to IFN-based therapies, one in relapse and one naïve) received treatment with DAAs (SVR: 100%). 3/11 patients increased their transfusion needs while 1/11 reported mild arthralgias. No drug-drug interactions between DAAs and chelation agents were observed as attested by the stability of ferritin levels during treatment., Conclusions: More than 1/3 of patients with haemoglobinopathies suffered from CHC. Response rates to IFN-based treatment seem to be similar to other patients with CHC, while most importantly, treatment with DAAs was excellent and safe even in difficult to treat patients (most null responders with severe fibrosis) suggesting that this group of HCV patients should no longer be regarded as a difficult to treat.

Background/aims: We found that pooled Crohn's disease (CD) sera strongly react with a human gap-junction connexin 37 (Cx37) peptide and tested for anti-Cx37 antibody reactivity in sera from CD patients and controls. We also investigated whether peptide-recognition is due to Cx37/microbial molecular mimicry., Methods: The PSI-BLAST program was used for Cx37(121-135)/microbial alignment. Reactivity to biotinylated human Cx37(121-135) and its microbial mimics was determined by ELISA using sera from 44 CD, 30 ulcerative colitis and 28 healthy individuals., Results: Anti-Cx37(121-135) reactivity (1/200 dilution) was present in 30/44 (68%) CD cases and persisted at 1/1000 dilution. Database search shows that Cx37(121-135) contains the -ALTAV- motif which is cross-recognized by diabetes-specific phogrin and enteroviral immunity. Testing of 9 Cx37(121-135)-microbial mimics revealed 57-68% reactivity against human enterovirus C, Lactococcus lactis, coxsackie virus A24 and B4. Anti-Cx37(121-135) was inhibited by itself or the microbial mimics. No reactivity was found against the poliovirus, rubella, and Mycobacterium tuberculosis mimics, or the beta cell phogrin autoantigen. Microbial/Cx37 reactivity was not able to differentiate CD patients from UC or healthy controls, in terms of overall prevalence and antibody titres, but microbial mimics were unable to inhibit reactivity to human Cx37 in the majority of the controls., Conclusions: Sera from CD patients react with connexin 37 and cross-react with specific Cx37-mimicking enteroviral peptides. Microbial/self reactivity can be seen in UC and healthy controls. The lack of responses to other Cx37(121-135) microbial mimics and the inability of the reactive microbes to inhibit reactivity to self is intriguing and warrants further investigation., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: In Greece, there are few data on the epidemiological characteristics of HBV. Our aim was to study the epidemiological patterns of HBV in Central Greece and identify the possible differences in HBV prevalence (clusters) among areas inside this region using data from the hepatitis registry., Methods: The study was performed in Thessaly, one out of the thirteen regions of Greece and covers most of the part of Central Greece. A total of 921 HBV patients were registered in the hepatitis registry during the period 1999-2004 while 303 were randomly selected to be studied further using a detailed questionnaire on several epidemiological factors., Results: 187/303 patients (61.7%) classified as chronic inactive HBV carriers, 78/303 (25.7%) had chronic hepatitis B, 29/303 (9.6%) had HBV-related cirrhosis and 9/303 (3%) HBV-related hepatocellular carcinoma (HCC). The route of HBV transmission was vertical in 103 (34%), sexual in 46 (15.1%) and intrafamilial in 98 (32.4%). Folk remedies were identified as the predisposing risk factor for contracting HBV infection in 38 (12.5%), previous transfusion in 9 (3%) and unknown mode of transmission in 9 patients (3%). Alcohol abuse was the only independent factor (OR: 2.5; p=0.01) associated with the progression to cirrhosis-HCC. There were specific areas (clusters) inside Thessaly region with increased ratio of HBV infection; Vertical and sexual modes of transmission were more prominent in some of these areas., Conclusions: Vertical, intrafamilial and sexual modes of HBV transmission identified as the major routes of HBV infection in our study. We also identified cluster areas of HBV infection in Central Greece. Alcohol abuse is frequent among HBV patients and is acting as an effect modificator risk factor for the development of HBV-related cirrhosis and HCC. Extended population studies in Greece are needed to assess in detail the epidemiological patterns of HBV and evaluate control programmes.

Background: Heart positioning during beating heart surgery produces significant haemodynamic compromise either when a deep pericardial stitch (DPS) or apical suction devices (ApSDs) are used. In this study the two techniques' haemodynamic performance and effect on intracardiac structures were compared through transoesophageal echocardiography (TEE) obtained volume measurements and three-dimensional ventricular and mitral valve computer reconstructions., Methods: Sequential 0 degrees to 180 degrees TEE images of the left heart were obtained in 10 patients undergoing beating heart surgery. Measurements with both techniques in three different positions were obtained: at baseline, the heart elevated to access its inferior surface and the heart elevated and rotated to access its lateral surface. Three-dimensional computer reconstructions of the mitral valve and the left heart were generated. Ventricular volume measurements were used to calculate stroke volume, ejection fraction and differences from baseline. An analysis of variance between each technique in all three positions was performed., Results: Central venous, left atrial and pulmonary artery pressures were significantly increased with either technique during positioning. Both techniques significantly affected left ventricular function decreasing stroke volume and ejection fraction. In the vertical and rotated position, the ApSD produced a significant decrease from baseline both in stroke volume (DPS: 32.8+/-18.7 vs ApSD: 55.46+/-21.7; p=0.02) and in ejection fraction (DPS: 19.3+/-10.5 vs ApSD: 40.9+/-24.6; p=0.02). The three-dimensional reconstructions demonstrated significant distortion of the atrioventricular geometry and the mitral valve, which was more pronounced with the DPS., Conclusion: Both techniques produce variable degrees of deformation with associated cardiac dysfunction and haemodynamic instability. Cardiac function is impeded more with an ApSD with the heart elevated and rotated.

Background: Hepatitis C virus (HCV) appears to be endemic in most parts of the world, but there is considerable geographic variation. In order to assess the geographic distribution of HCV in Thessaly, in central Greece, we conducted a retrospective study in HCV-infected patients attending the Academic Liver Unit of Thessaly University from 1999 to 2003. We also investigated whether variation among regions could be attributed to differences in risk factors., Methods: We evaluated the records of 309 HCV patients whose origin and/or residence was in Thessaly. To identify risk factors that were independently associated with the place of birth and/or residence, adjusted odds ratios (OR) were calculated by logistic regression analysis. We also studied the medical records of 150 HCV-negative patients from the same areas in order to evaluate whether there are differences in risk factors reported by HCV-positive and HCV-negative patients., Results: We found three municipalities with a high HCV frequency. The use of non-disposable, multiple-use glass syringes for medical purposes in the past was the only potential risk factor more frequently identified in these areas than in other places (OR=2.3; p<0.05). This risk factor was significantly (p<0.001) associated with older age of the infected patients., Conclusions: This study shows that the spread of HCV in the three regions may have occurred several years ago as a result of the use of multiple-use glass syringes. Differences in prevalence rates among different age groups, as well as among different areas, indicate the need for extensive studies to determine HCV epidemiology and to develop appropriate prevention programs.

We studied the prevalence and clinical significance of anticardiolipin antibodies (aCL) in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) as similar data are missing. Ninety-nine PBC patients, 41 PSC, 228 HCV, 50 HBV, 111 with other non-viral and non-autoimmune liver disorders and 267 healthy were investigated. In order to evaluate the avidity of aCL, urea 2 M was used. IgG and/or IgM aCL were detected in 40% of PBC and PSC patients, in 26.2% of disease controls (P < 0.05) and 2.25% of healthy (P < 0.05). In PBC, IgG aCL associated with presence of cirrhosis, increased Mayo risk score and thrombocytopenia, while in PSC with longer disease duration and biochemical activity. Anti-beta2-GPI was detected in only three patients. Both in PBC and PSC, resistance of aCL to urea was high, similar to that observed in antiphospholipid syndrome (APS). We demonstrated a significantly higher prevalence of aCL in PBC and PSC compared to other liver diseases and healthy. aCL were associated with more severe disease in PBC and biochemical activity in PSC, but they rather seem to be "non-pathogenic" (co-factor-independent). However, their avidity was comparable with that of APS, indicating the need for prospective studies in order to address whether aCL in PBC and PSC may contribute to APS development or the progression of hepatic disease.

Hepatopulmonary syndrome (HPS) is defined as a clinical triad including liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations. We report a 61-year-old male presented with fatigue, long-lasting fever, loss of weight, signs of portal hypertension, hepatosplenomegaly, cholestasis and progressive dyspnoea over the last year. Clinical, laboratory and histological findings confirmed the diagnosis of granulomatous hepatitis. HPS due to hepatic granuloma-induced portal hypertension was proved to be the cause of severe hypoxemia of the patient as confirmed by contrast-enhanced echocardiography. Reversion of HPS after corticosteroid therapy was confirmed by a new contrast-enhanced echocardiography along with the normalization of cholestatic enzymes and improvement of the patient's conditions. This is the first case of complete reversion of HPS in a non-cirrhotic patient with hepatic granuloma, indicating that intrapulmonary shunt in liver diseases is a functional phenomenon and HPS can be developed even in miscellaneous liver involvement as in this case.

Autoimmune hepatitis (AIH) is a chronic necroinflammatory disease of the liver characterized by hypergammaglobulinemia, characteristic autoantibodies, association with HLA DR3 or DR4 and a favorable response to immunosuppressive treatment. The etiology is unknown. The detection of non-organ and liver-related autoantibodies remains the hallmark for the diagnosis of the disease in the absence of viral, metabolic, genetic, and toxic etiology of chronic hepatitis or hepatic injury. The current classification of AIH and the several autoantibodies/target-autoantigens found in this disease are reported. Current aspects on the significance of these markers in the differential diagnosis and the study of pathogenesis of AIH are also stated. AIH is subdivided into two major types; AIH type 1 (AIH-1) and type 2 (AIH-2). AIH-1 is characterized by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Determination of antineutrophil cytoplasmic autoantibodies (ANCA), antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies against to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of patients who are seronegative for ANA/SMA. AIH-2 is characterized by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). Cytochrome P450 2D6 (CYP2D6) has been documented as the major target-autoantigen of anti-LKM-1 autoantibodies in both AIH-2 and HCV infection. Recent convincing data demonstrated the expression of CYP2D6 on the surface of hepatocytes suggesting a pathogenetic role of anti-LKM-1 autoantibodies for the liver damage. Family 1 of UDP-glycuronosyltransferases has been identified as the target-autoantigen of anti-LKM-3. For these reasons the distinction between AIH and chronic viral hepatitis (especially of HCV) is of particular importance. Recently, the molecular target of anti-SLA/LP and anti-LC1 autoantibodies were identified as a 50 kDa UGA-suppressor tRNA-associated protein and a liver specific enzyme, the formiminotransferase cyclodeaminase, respectively. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate closely with disease severity and response to treatment suggesting a pathogenetic role of these autoantibodies for the hepatocellular injury. In general however, autoantibodies should not be used to monitor treatment, predict AIH activity or outcome. Finally, the current aspects on a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) are also given. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies detected in AIH as a disease component of APECED but also in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target-autoantigen of anti-LM autoantibodies in both APECED-related AIH and dihydralazine-induced hepatitis. The latter may indicate that similar autoimmune pathogenetic mechanisms can lead to liver injury in susceptible individuals irrespective of the primary defect. Characterization of the autoantigen-autoantibody repertoire continues to be an attractive and important tool to get access to the correct diagnosis and to gain insight into the as yet unresolved mystery of how hepatic tolerance is given up and AIH ensues.

Background: The mechanisms by which interferon-gamma (IFN-gamma) contributes to inter-individual heterogeneity in the severity of chronic hepatitis C (CH-C) are unknown. In 116 consecutive patients with CH-C, we tested the hypothesis that host genetic factors regulating IFN-gamma production and activity influence the severity of liver damage and hepatitis C virus (HCV)-specific T-cell reactivity., Methods: We determined the genotypes of functionally significant polymorphisms in the IFN-gamma gene and in the promoter of interleukin-10 (IL-10), a cytokine that counteracts IFN-gamma. We also measured concanavalin A (Con A)-stimulated IL-10 and IFN-gamma production, and the frequency of virus-specific T-cells, producing IFN-gamma or IL-10., Results: The grade of inflammation and the stage of fibrosis of CH-C showed no associations with either the IFN-gamma or IL-10 promoter polymorphisms or with Con A-stimulated IL-10 or IFN-gamma production. Similarly, there were no associations between HCV-specific T-cell frequencies and these host genetic factors. On multivariate analysis, the grade of inflammation and the duration of HCV infection accounted for only 37% of the variance in the stage of CH-C (P<0.0001). This percentage did not increase by including any genetic variables in the analyses., Conclusion: Future studies investigating the entire cytokine gene sequences will provide better information regarding genetic variations responsible for inter-individual differences in the severity of CH-C., (Copyright Blackwell Munksgaard 2004)

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the destruction of biliary epithelial cells, presumably by autoimmune mechanism(s). Although lymphocytes play a pivotal role in the pathogenesis of PBC, the possible involvement of eosinophils has also been suggested. Recent studies have shown that eosinophilia possibly occurs in the peripheral blood of PBC patients. We present four cases of asymptomatic middle-aged women with moderate-to-high eosinophilia observed during random investigation. Alkaline phosphatase (ALP) was increased in two of them. As a result of clinical and laboratory evaluations the early stages of PBC were diagnosed in all the patients, as attested by the detection of high titres of anti-mitochondrial antibodies and the characteristic lesions on liver biopsies. Liver function tests and eosinophils returned within normal limits after 2 months of treatment with ursodeoxycholic acid, suggesting that its potential immunomodulatory actions may extend to eosinophils. Our report further supports the possibility that eosinophilia may occur in PBC, especially in its early stages. From the clinical point of view, we believe that PBC should be considered in the differential diagnosis of eosinophilia with an otherwise unknown origin. In particular, PBC should be suspected in a patient when other causes of eosinophilia have been excluded, irrespective of the presence or absence of symptoms, or the presence or absence of elevated ALP. In such cases further evaluation for anti-mitochondrial antibodies should be done. These observations might assist the development of future therapeutic concepts in the management of PBC, at least for patients in early stages of the disease.