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Although a prophylactic vaccine is available, hepatitis B virus (HBV) remains a major cause of liver-related morbidity and mortality. Current treatment options are improving clinical outcomes in chronic hepatitis B; however, true functional cure is currently the exception rather than the rule. Nucleic acid vaccines are among the emerging immunotherapies that aim to restore weakened immune function in chronically infected hosts. DNA vaccines in particular have shown promising results in vivo by reducing viral replication, breaking immune tolerance in a sustained manner, or even decimating the intranuclear covalently closed circular DNA reservoir, the hallmark of HBV treatment. Although DNA vaccines encoding surface antigens administered by conventional injection elicit HBV-specific T cell responses in humans, initial clinical trials failed to demonstrate additional therapeutic benefit when administered with nucleos(t)ide analogs. In an attempt to improve vaccine immunogenicity, several techniques have been used, including codon/promoter optimization, coadministration of cytokine adjuvants, plasmids engineered to express multiple HBV epitopes, or combinations with other immunomodulators. DNA vaccine delivery by electroporation is among the most efficient strategies to enhance the production of plasmid-derived antigens to stimulate a potent cellular and humoral anti-HBV response. Preliminary results suggest that DNA vaccination via electroporation efficiently invigorates both arms of adaptive immunity and suppresses serum HBV DNA. In contrast, the study of mRNA-based vaccines is limited to a few in vitro experiments in this area. Further studies are needed to clarify the prospects of nucleic acid vaccines for HBV cure.

Interleukin-33 (IL-33) is a cytokine defined by its pleiotropic function, acting either as a typical extracellular cytokine or as a nuclear transcription factor. IL-33 and its receptor, suppression of tumorigenicity 2 (ST2), interact with both innate and adaptive immunity and are considered critical regulators of inflammatory disorders. The IL-33/ST2 axis is involved in the maintenance of intestinal homeostasis; on the basis of their role as pro- or anti-inflammatory mediators of first-line innate immunity, their expression is of great importance in regard to mucosal defenses. Mucosal immunity commonly presents an imbalance in inflammatory bowel disease (IBD). This review summarizes the main cellular and molecular aspects of IL-33 and ST2, mainly focusing on the current evidence of the pro- and anti-inflammatory effects of the IL-33/ST2 axis in the course of ulcerative colitis and Crohn’s disease, as well as the molecular mechanisms underlying the association of IL-33/ST2 signaling in IBD pathogenesis. Although IL-33 modulates and impacts the development, course, and recurrence of the inflammatory response, the exact role of this molecule is elusive, and it seems to be associated with the subtype of the disease or the disease stage. Unraveling of IL-33/ST2-mediated mechanisms involved in IBD pathology shows great potential for clinical application as therapeutic targets in IBD treatment.

Background: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. Methods: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. Results: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86–0.91)]. Cronbach’s coefficient alpha for all items achieved 0.90 (95%CI 0.88–0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. Conclusions: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.

Background/aim The present study was undertaken to investigate (i) whether hospitalized patients with COVID-19 pneumonia present intestinal barrier dysfunction with consequent translocation of endotoxin into the systemic circulation and (ii) whether intestinal barrier biomarkers have any prognostic role in terms of progression to severe respiratory failure. Patients and methods In this prospective study, 22 patients with COVID-19-associated pneumonia and 19 patients with non-COVID-19-related community-acquired pneumonia (CAP group) were studied while 12 healthy persons comprised the control group. Blood samples were collected on admission and analysed for serum levels of endotoxin and zonula occludens-1 (ZO1). Clinical courses regarding progression to severe respiratory failure (SRF) requiring mechanical ventilation were recorded. Results Patients with COVID-19-associated pneumonia and patients with CAP presented significantly higher serum endotoxin and ZO1 concentrations on admission as compared to healthy controls. There was no difference in endotoxin levels between patients with COVID-19-related pneumonia and patients with CAP. In patients with COVID-19-related pneumonia, serum endotoxin concentrations were positively correlated with C-reactive protein and ferritin values. There were no significant differences in serum endotoxin and ZO1 concentrations between patients with severe and not severe COVID-19-related pneumonia, nor between patients who developed SRF and those who did not Conclusion: Patients with COVID-19-related pneumonia present intestinal barrier dysfunction leading to systemic endotoxemia. Admission values of endotoxin and ZO1 do not have any prognostic role for progression to SRF.

There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D–VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D–VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.

Acute upper gastrointestinal bleeding (AUGIB) remains a common medical emergency with considerable morbidity and mortality. The aim of this study was to describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with AUGIB nowadays and compare these with those of patients 15 years ago.This was a single-center survey of adults (16 years) presenting with AUGIB to a tertiary hospital. Data from 401 patients presenting with AUGIB in a tertiary hospital between January 1, 2019 and December 31, 2020 were analyzed and compared with data from 434 patients presenting with AUGIB at the same hospital between January 1, 2004 and December 31, 2005.Nowadays, patients were older, mean age was 69.5 (± 15.4) vs. 66.2 (± 16.0) years, they had more frequently coexisting diseases (83.5% vs. 72.8%), especially cardiovascular diseases (62.3% vs. 52.5%), and more individuals were inpatients at onset of bleeding (8.2% vs. 4.1%). In addition, more patients were under anticoagulants (18.5% vs. 6.2%), but less were under acetylsalicylic acid ± clopidogrel (36.9% vs. 33.9%). Carlson Comorbidity Index was higher nowadays (5.6 ± 6.4 vs. 3.4 ± 2.3). Moreover, a peptic ulcer was less frequently found as the cause of bleeding (38.4% vs. 56.9%), while more often nowadays endoscopy was negative (12.7% vs. 3.5%). In patients with peptic ulcer, active bleeding on endoscopy was less frequent (7.1% vs. 14.2%). Also, bleeding spots requiring hemostasis were less common on endoscopy (39.6% vs. 49.4%) and more patients were without spots of recent bleeding (49.4% vs. 38.9%). Finally, the rate of rebleeding statistically decreased (7.8% vs. 4.2%), while overall mortality remained relatively unchanged (5.0% vs. 6.2%).AUGIB episodes nowadays are less severe with less peptic ulcer bleeding, but the patients are older and with more comorbidities.

Background Adherence and persistence to long-term therapy with nucleos(t)ides analogues are crucial to the outcome of treatment in chronic hepatitis B. Our aim was to determine the persistence and adherence rates to nucleos(t)ides analogues in chronic hepatitis B patients under maintenance therapy and to identify relative to prediction of adherence factors. Methods We retrospectively analyzed electronic prescription data of patients (2011-2016; n = 400) with chronic hepatitis B treated with nucleos(t)ides analogues at 4 tertiary liver centers in Greece. Results Two hundred ninety-six of 400 patients were under or initiated treatment in 2011-2012 (existing patients), while the remainder initiated or switched medication from January 2013 and onward (new patients). The median adherence rate was 99%, with 89.7% achieving adherence >80% during a mean follow-up of 28 ± 14 months. The overall 12-month persistence rate was 57%, with no difference between patients receiving tenofovir, entecavir or double therapy (57.8%, 52.8% and 68.4%, respectively, P = 0.399). The decline in persistence was more pronounced during the first 3 months of follow-up and in existing patients (P = 0.057). Overall, 80% and 55.1% of nonpersistent patients succeeded adherence to nucleos(t)ides analogues >80% and >90%, respectively. Multivariate analyses showed that existing (vs. new) patients were less likely to have >80% adherence (odds ratio: 0.324, P = 0.44) and persistence (odds ratio: 0.562, P = 0.057) to nucleos(t)ides analogues therapy. Conclusion In this real-world cohort of chronic hepatitis B patients, high adherence to nucleos(t)ides analogues was coupled with suboptimal persistence with prescribing the medication. Our data indicate that persistence and adherence are distinct measures that should be approached separately in educational programs targeting to improve medication-taking behavior in chronic hepatitis B.

Non-alcoholic fatty liver disease is a highly prevalent medical condition, characterized by intrahepatic fat accumulation which may eventually lead to hepatic inflammation, cell death and reactive fibrosis. Obesity and metabolic disturbances constitute significant contributors to liver steatosis pathogenesis, however, there is a growing awareness that fatty liver may emerge even in normal weight or metabolically healthy individuals. In recent years, advanced imaging techniques have revealed that liver steatosis is quite common in inflammatory bowel disease patients, suggesting that intestinal inflammation and disturbances of the liver-gut axis may also play a key role in non-alcoholic fatty liver disease pathophysiology. The current review focuses on the co-occurrence of the two disorders, integrating research findings on epidemiology, clinical characteristics and common pathophysiological processes. The study of liver steatosis in inflammatory bowel disease patients may provide useful insights on the complex links between dietary fat intake, metabolic dysregulation, gut physiology and intrahepatic cellular mechanisms underlying liver inflammation and damage.

The measurement of total and free cortisol has been studied as a clinical index of adrenal cortisol production in patients with liver cirrhosis. Correlations between free plasma and salivary cortisol have previously been reported in stable cirrhotic patients. Urinary free cortisol constitutes an index of adrenal cortisol production; however, it has never been used in assessing adrenal function in patients with liver cirrhosis.The aim of this observational study was to determine associations between urinary free cortisol, serum total, salivary, measured and calculated plasma free cortisol levels in cirrhotics, determining which of them can be used as an indirect index of free cortisol levels. Moreover, we investigated the potential use of 24 h urinary free cortisol as a prognostic factor for mortality.Seventy-eight outpatients with liver cirrhosis were included. Serum, salivary and urinary free cortisol were measured using the electrochemiluminenscence immunoassay. Plasma free cortisol determination was conducted using a single quadrupole mass spectrometer. The quantification of free cortisol was achieved by determining the signal response on negative ESI-MS mode.Twenty-four hour urinary free cortisol levels correlated with free cortisol determined by mass spectrometer, total cortisol and calculated free cortisol levels. Patients with low levels of urinary free cortisol presented a significantly higher mortality rate compared to those with high levels. The factors associated with death risk were determined by Cox regression. In the multivariate analysis, two models were applied; in the first model, CP score, PVT and urinary free cortisol were found to be significantly related to patients' survival, whereas in the second, MELD score, ascites and urinary free cortisol were independently related to survival.This study suggests that 24 h urinary free cortisol could be considered as a potential index of adrenal cortisol production in patients with liver cirrhosis and it potentially detects patients with a high mortality risk.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Vitamin D and its receptor (VDR) exert important immunoregulatory functions that contribute to liver homeostasis. The aim of this study was to investigate the influence of FokI, ApaI, BsmI and TaqI VDR polymorphisms on cirrhosis development and laboratory variables in patients with chronic hepatitis C (CHC).A total of 48 patients were enrolled in this retrospective, observational study and underwent genotype analysis; their medical records were examined to obtain relevant data.The cumulative rate of progression to cirrhosis during the course of CHC was 31.3% after a median period of 11 years from diagnosis. Importantly, in multivariate analysis, FokI ff (adjusted hazard ratio [aHR] 13.6, 95% confidence interval [CI] 2.51-73.73; P=0.002) and ApaI aa (aHR 4.69, 95%CI 1.13-19.43; P=0.033) genotypes were independently associated with progression to cirrhosis. The presence of the aa genotype was also associated with higher liver stiffness measurements measured by transient elastography compared to the AA/Aa genotype (12.3kPa interquartile range [IQR] 9.6-17.3 vs. 7.1kPa IQR 5.6-11.1; P=0.012). In addition, higher HCV RNA and lower serum albumin levels were observed in patients with the tt genotype of the TaqI polymorphism compared to TT/Tt carriers, and in patients with the aa genotype compared to AA/Aa carriers. In haplotype analysis, no association was found between any haplotype and disease progression.In patients with CHC, laboratory parameters are influenced by VDR polymorphisms and the development of cirrhosis is related to homozygosity for the dominant trait of ApaI and FokI variants.

Objective(s) Increasing evidence indicates that vitamin D status is linked to severity of liver cirrhosis and patients' survival. However, the potential role of vitamin D-related immunomodulation in hepatic decompensation and patients' mortality in relation to vitamin D deficiency remains unknown. The aim of the current study is to evaluate the association between vitamin D status and vitamin D binding protein (VDBP) levels with serum cytokine and lipopolysaccharide binding protein (LBP) and to examine their role on disease severity and cirrhotics' mortality. Methods One hundred consecutive Caucasian patients with liver cirrhosis were enrolled in the study. 25(OH)D, VDBP, and LBP concentrations were assessed by ELISA. Cytokine tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), IL-1β, IL-8, IL-10, and IL-12 levels were determined by Cytometric Bead Array. Results 25(OH)D levels were inversely correlated with CP score, MELD, IL-6, and CP stage and VDBP levels with CP score, MELD, IL-6, IL-8, LBP, and CP stage. Cirrhotics with 25(OH)D deficiency and severe deficiency had significantly higher CP score, increased IL-6 levels and lower VDBP levels. In the multivariate analysis, the independent prognostic factors associated with patients' survival were CP stage B [hazard ratio = 6.75; 95% confidence interval (CI) 1.32, 34.43; P = 0.022], CP stage C (hazard ratio = 7.39; 95% CI 1.41, 38.81; P = 0.018), the presence of hepatocellular carcinoma (hazard ratio = 4.50; 95% CI 1.54, 13.13; P = 0.006) and 25(OH)D levels (hazard ratio = 0.87; 95% CI 0.80, 0.95; P = 0.002). Conclusion The results show that vitamin D status and VDBP levels are associated with liver cirrhosis severity and patients' mortality, possibly through a proinflammatory immune response.

Inflammasomes are multiprotein intracellular complexes which are responsible for the activation of inflammatory responses. Among various subtypes of inflammasomes, NLRP3 has been a subject of intensive investigation. NLRP3 is considered to be a sensor of microbial and other danger signals and plays a crucial role in mucosal immune responses, promoting the maturation of proinflammatory cytokines interleukin 1β (IL-1β) and IL-18. NLRP3 inflammasome has been associated with a variety of inflammatory and autoimmune conditions, including inflammatory bowel diseases (IBD). The role of NLRP3 in IBD is not yet fully elucidated as it seems to demonstrate both pathogenic and protective effects. Studies have shown a relationship between genetic variants and mutations in NLRP3 gene with IBD pathogenesis. A complex interaction between the NLRP3 inflammasome and the mucosal immune response has been reported. Activation of the inflammasome is a key function mediated by the innate immune response and in parallel the signaling through IL-1β and IL-18 is implicated in adaptive immunity. Further research is needed to delineate the precise mechanisms of NLRP3 function in regulating immune responses. Targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies.

Escherichia coli (E. coli) is a rare cause of infective endocarditis, despite being a common cause of bacteremia. E. coli endocarditis affects most frequently immunocompromised elderly women, especially those with diabetes mellitus. We present a case of a 78-year-old female immunocompetent patient, presenting with septic shock and multiple organ dysfunction syndrome. E. coli was isolated in all sets of blood cultures and in urine culture and a contrast-enhanced abdominal computed tomography (CT) scan revealed spleen and left kidney infracts. Transthoracic echocardiography revealed a large (> 15 mm) mobile mass on the atrial side of the posterior mitral valve leaflet. The patient was initially treated with intravenous ceftriaxone and ciprofloxacin for 2 weeks with successful clinical response and clearance of bacteremia, was then subjected to valve replacement (with isolation of E. coli from replaced valve cultures) and continued antibiotic therapy for additional 4 weeks postoperatively. E. coli has emerged in recent years as an important cause of bacteremia, especially in the elderly. In selected patients, as those with persistent Gram-negative bacteremia or severe sepsis/septic shock, echocardiography is of paramount importance for the diagnosis of Gram-negative endocarditis and should be included in our diagnostic algorithm of patient’s evaluation.

There is growing evidence of vitamin D involvement in immune regulation and gut barrier function, suggesting that vitamin D may play a critical role in the development of inflammatory bowel disease (IBD). This review presents advances in the molecular mechanisms of vitamin D and vitamin D receptor (VDR) signaling with respect to barrier integrity and innate/adaptive immunity in the gut, as well as recent findings in uncovering the biological link between vitamin D-associated genetic variants and IBD. Experimental data have revealed a mechanistic basis for the contribution of vitamin D to the pathogenesis of IBD. The vitamin D/VDR complex is involved in the regulation of innate and adaptive immune responses to pathogenic threats by acting as an immunomodulator and alleviating inflammation in experimental IBD models and IBD patients, contributing to intestinal homeostasis. Vitamin D has been associated with the promotion of antimicrobial peptide secretion, down-regulation of dendritic cell activity, induction of tolerogenic rather than pro-inflammatory T-cell differentiation and function, and increased production of anti-inflammatory cytokines, highlighting its potential therapeutic value for IBD. Elucidating the complex interplay between vitamin D/VDR and the pathogenesis of IBD is critical for the development of novel therapeutic interventions and for the potential use of this molecule as a prognostic and diagnostic tool in clinical practice.

The role of patients' metabolic clinical and biochemical profile in NAFLD has not been extensively explored.The aim of the study was to assess the role of metabolic health in NAFLD patients and to examine liver disease progression in these populations.The medical charts of 569 patients diagnosed with fatty liver were thoroughly reviewed; 344 patients were excluded because of other chronic liver diseases. Metabolically healthy people were defined as those who met none of the following criteria: blood pressure ≥ 130/85 mmHg or under hypertension treatment, fasting glucose ≥ 100 mg/dl or under diabetes treatment, serum triglycerides150 mg/dl, high density lipoprotein-cholesterol40/50 mg/dl for men/women. Study participants were followed-up over a median period of 22 months.The present observational case-control study included 225 NAFLD patients; 14 (6.2%) were metabolically healthy. Metabolically healthy participants were younger (p = 0.006), had lower age at diagnosis (p = 0.002), lower levels of γ-GT (p = 0.013), fasting glucose (p 0.001) and triglycerides (p 0.001) and higher HDL-cholesterol (p = 0.005) compared to metabolically non-healthy. By the last follow up assessment, 8 metabolically healthy patients had developed dyslipidemia; 1 patient (14.4%) had presented liver disease progression compared to 8 patients (10.5%) from the unhealthy group (p = 0.567). In multivariate analysis, diabetes mellitus (p = 0.017) and hemoglobin levels (p = 0.009) were the sole independent predictors of disease progression. No significant difference was observed in liver disease progression-free survival rates among the two patient groups (p = 0.503).Metabolically healthy NAFLD patients presented with a favorable biochemical profile; however, they were diagnosed with NAFLD at a younger age and the liver disease progression risk was similar to that of metabolically unhealthy patients. These findings suggest that metabolically healthy NAFLD may not constitute a benign condition and patients could potentially be at increased risk of metabolic syndrome and liver disease progression.

Background: Leptospirosis is a zoonosis with global distribution. The aim of the present study was to determine epidemiological, clinical and laboratory characteristics of leptospirosis in Greece.M...

BACKGROUND & AIMS Discontinuation of nucleos(t)ide analogues (NA) remains a debatable issue in HBeAg-negative chronic hepatitis B (CHB). This study aimed to address the outcome of HBeAg-negative CHB patients who discontinued NA therapy. METHODS This prospective study included 57 non-cirrhotic HBeAg-negative Caucasian CHB patients who discontinued NA therapy after median virological remission of 6 years. All patients had regular blood tests. Virological relapse was defined as HBV DNA > 2000 IU/mL or >20 000 IU/mL and biochemical relapse as ALT > ULN (40 IU/mL) or >2xULN. All patients with retreatment predefined criteria restarted entecavir or tenofovir. RESULTS Of the 57 patients, 29 remained without retreatment after median follow-up of 65 months (range: 36-87) following treatment discontinuation. At 3, 6, 12, 24, 36 and 48 months, cumulative rates of retreatment were 16%, 20%, 32%, 35%, 46% and 50%, while the proportion of patients with HBV DNA

Background No evidence is available on the natural history of grade 1 ascites and its progression to grade 2/3 in patients with liver cirrhosis. The aim of the current study was to address this issue, to assess the development of main comorbid disorders closely related to ascites progression, and to identify the predictive factors for survival in this setting. Methods Consecutive Caucasian cirrhotic patients with grade 1 ascites were retrospectively analyzed. None of patients was under treatment with diuretics at diagnosis. Control groups consisted of 145 cirrhotics with grade 2/3 ascites and 175 cirrhotics without ascites. Results Diuretics were initiated in 58 patients with grade 1 ascites at baseline by the attending physician. At the last follow up, 29 patients had no ascites, 33 patients had grade 1 and 38 patients had grade 2/3 ascites. No variable was found to be an independent predictor of grade 2/3 ascites. Seven patients developed spontaneous bacterial peritonitis while under treatment with diuretics; at that time only 1 patient had grade 1 ascites. The mortality rate was similar among all examined groups. Conclusions This study suggests that the presence of grade 1 ascites does not constitute a precursor of grade 2/3 ascites in patients with cirrhosis. Thus, patients with grade 1 ascites do not require specific treatment with diuretics.

Background Long-term monotherapy with nucleos(t)ide analogs (NAs) represents the treatment option for the majority of patients with chronic hepatitis B (CHB), an aging population with a greater likelihood of comorbidities. We assessed the prevalence of concurrent non-hepatic diseases and the safety monitoring in a large cohort of CHB patients receiving NAs and their potential impact on disease outcomes. Methods We included 500 consecutive CHB patients from 5 major tertiary Greek centers, under long-term therapy with an NA. Epidemiological/clinical characteristics and data on concomitant disease, drug use and investigations ordered were collected. Results The mean age was 58 years and 66% were male. Most patients were receiving tenofovir disoproxil fumarate (TDF, 60%) or entecavir (ETV, 37%) monotherapy. Decompensated cirrhosis at baseline was present in 10%, while hepatocellular carcinoma (HCC) under therapy developed in 21 patients. The median duration of total NA therapy was 56 and of latest therapy 42 months. The most common (prevalence >10%) comorbidities were hypertension (28%), non-HCC cancer(s) (12%), and diabetes (11%). Patients with a longer duration of latest therapy (≥4 vs.

Objective Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent medical condition, which may lead to severe complications including cirrhosis and hepatocellular carcinoma. Its chronic course and its association with obesity and diabetes mellitus augment the long-term impact of NAFLD on patients' health and quality of life (QoL) and put great strain on healthcare systems worldwide. Research is growingly focusing on NAFLD patients' QoL in an attempt to describe the full spectrum of disease burden and tackle its future consequences. Relevant studies are characterized by sample heterogeneity and provide conflicting findings which should be interpreted with the use of a systematic and integrative approach. In this context, our aim was to conduct a systematic literature review on the topic of NAFLD patients' QoL. Methods We performed a systematic search of PubMed, ScienceDirect and GoogleScholar databases according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results Our search yielded 14 suitable articles reporting data from almost 5000 patients. All authors agree that NAFLD patients' QoL is impaired especially in the physical sub-domain. In addition, several demographic, clinical and histopathological parameters have emerged as major determinants of patients' QoL. However, future studies are needed to further clarify these issues. Conclusions NAFLD patients report poor physical QoL. QoL impairment is associated with a variety of disease-related parameters, mostly the presence of fatigue and cirrhosis.

Gut permeability is increased in critically ill patients, and associated with the development of the systemic inflammatory response syndrome and multiple organ dysfunction syndrome (MODS). The pathogenetic link(s) and potential therapies are an area of intense research over the last decades. We thoroughly reviewed the literature on gut-origin sepsis and MODS in critically ill patients, with emphasis on the implicated pathophysiological mechanisms and therapeutic interventions. Intestinal barrier failure leading to systemic bacterial translocation associated with MODS was the predominant pathophysiological theory for several years. However, clinical studies with critically ill patients failed to provide the evidence of systemic spread of gut-derived bacteria and/or their products as a cause of MODS. Newer experimental data highlight the role of the mesenteric lymph as a carrier of gut-derived danger-associated molecular patterns (DAMPs) to the lung and the systemic circulation. These substances are recognized by pattern recognition receptor-bearing cells in diverse tissues and promote proinflammatory pathways and the development MODS. Therefore, the gut becomes a pivotal proinflammatory organ, driving the systemic inflammatory response through DAMPs release in mesenteric lymph, without the need for systemic bacterial translocation. There is an emerging need for application of sensitive non-invasive and easily measured biomarkers of early intestinal injury (e.g., citrulline, intestinal fatty acid protein, and zonulin) in our everyday clinical practice, guiding the early pharmacological intervention in critically ill patients to restore or prevent intestinal injury and improve their outcomes.

Aim To summarize and critically examine the role of band ligation in secondary prophylaxis of variceal bleeding in patients with cirrhosis. Methods A literature review was performed using the MEDLINE and PubMed databases. The search terms consisted of the words "endoscopic band ligation" OR "variceal band ligation" OR "ligation" AND "secondary prophylaxis" OR "secondary prevention" AND "variceal bleeding" OR "variceal hemorrhage" AND "liver cirrhosis". The data collected from relevant meta-analyses and from the most recent randomized studies that were not included in these meta-analyses were used to evaluate the role of endoscopic band ligation in an effort to demonstrate the most recent advances in the treatment of esophageal varices. Results This study included 11 meta-analyses published from 2002 to 2017 and 10 randomized trials published from 2010 to 2017 that evaluated the efficacy of band ligation in the secondary prophylaxis of variceal bleeding. Overall, the results proved that band ligation was superior to endoscopic sclerotherapy. Moreover, the use of β-blockers in combination with band ligation increased the treatment effectiveness, supporting the current recommendations for secondary prophylaxis of variceal bleeding. The use of transjugular intrahepatic portosystemic shunt was superior to combination therapy regarding rebleeding prophylaxis, with no difference in the survival rates; however, the results concerning the hepatic encephalopathy incidence were conflicting. Recent advances in the management of secondary prophylaxis of variceal bleeding have targeted a decrease in portal pressure based on the pathophysiological mechanisms of portal hypertension. Conclusion This review suggests that future research should be conducted to enhance current interventions and/or to develop innovative treatment options with improved clinical endpoints.