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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.

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.

Aim To identify factors predicting mucosal healing in ulcerative colitis patients treated with anti-TNFα agents with or without azathioprine. Methods In a prospective, multicenter, one-year study biologic naive patients aged 25–65 years, with corticosteroid-dependent or refractory colitis received combination treatment with anti-TNFα and azathioprine for 6 months followed by anti-TNFα monotherapy. Patients who denied combination therapy or were outside this age range received anti-TNFα monotherapy (controls). Before and at weeks 12 and 54 of treatment the total Mayo score was calculated. Mucosal healing was defined as endoscopic subscore of 0. Mucosal expression of T helper (Th) cell-lineage specific transcription factors (Tbet, Gata3, Rorc, FoxP3) before treatment was also associated with mucosal healing. Results Of 67 patients, 58 (86.6%) received combination and 9 (13.4%) anti-TNFα monotherapy. Overall 29 (43.3%) patients achieved mucosal healing; rates were higher in patients receiving combination therapy vs. monotherapy (p = 0.03) and in azathioprine naive vs. exposed patients in the combination group (p = 0.01). Mucosal healing was associated with lower pre-treatment mucosal expression of transcription factor Th1–Tbet (p Conclusions Mucosal healing was associated with combination therapy, especially in biologic and azathioprine-naive patients and pre-treatment mucosal expression of specific Th specific transcripting factors (Tbet and Rorc).

The human intestinal microbiota coevolves with its host through a symbiotic relationship and exerts great influence on substantial functions including aspects of physiology, metabolism, nutrition and regulation of immune responses leading to physiological homeostasis. Over the last years, several studies have been conducted toward the assessment of the host-gut microbiota interaction, aiming to elucidate the mechanisms underlying the pathogenesis of several diseases. A defect on the microbiota-host crosstalk and the concomitant dysregulation of immune responses combined with genetic and environmental factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). To this end, novel therapeutic options based on the gut microbiota modulation have been an area of extensive research interest. In this review we present the recent findings on the association of dysbiosis with IBD pathogenesis, we focus on the role of gut microbiota on the treatment of IBD and discuss the novel and currently available therapeutic strategies in manipulating the composition and function of gut microbiota in IBD patients. Applicable and emerging microbiota treatment modalities, such as the use of antibiotics, prebiotics, probiotics, postbiotics, synbiotics and fecal microbiota transplantation (FMT) constitute promising therapeutic options. However, the therapeutic potential of the aforementioned approaches is a topic of investigation and further studies are needed to elucidate their position in the present treatment algorithms of IBD.

BACKGROUND/AIMS: Lamivudine improves liver histology in patients with chronic hepatitis B (CHB), but its effects on portal pressure remain unknown. We evaluated the effect of lamivudine monotherapy on hepatic venous pressure gradient (HVPG) in CHB-related cirrhosis with significant portal hypertension. METHODS: We studied 19 patients with cirrhosis due to HBeAg-negative CHB and HVPG >or=10 mm Hg treated with oral lamivudine (100mg daily). Liver biochemistry, Child-Pugh and MELD score were determined every 3 months, alpha-fetoprotein and HBV DNA every 6 months and HVPG at baseline and at 12 months after lamivudine initiation. Diuretics, beta-blockers, antibiotics and/or endoscopic therapy were used for routine indications. RESULTS: At 12 months, a significant reduction was observed in ALT (p=0.001), HBV DNA (p=0.002), Child-Pugh (p=0.012) and MELD score (p=0.006). Four patients developed virological breakthrough during treatment. At 12 months, HVPG decreased in all but one patient [baseline: 14.4+/-3.9 and 12 months: 12.4+/-3.3 mm Hg (p=0.007)]. HVPG decreased >20% or below the 12 mm Hg threshold in 10 of 13 patients with baseline HVPG >or=12 mm Hg. HVPG increased in a patient with hepatic flare after virological breakthrough. CONCLUSION: In conclusion, in patients with cirrhosis due to HBeAg-negative CHB, lamivudine monotherapy reduces HVPG, especially when virological suppression and biochemical remission is achieved.

Variceal bleeding is a serious complication in patients with cirrhosis. Although bleeding related mortality rates have fallen recently, it continues to be amongst the leading causes of death. Cirrhotics should be screened for varices at diagnosis. Data on preventing formation/growth of oesophageal varices (pre-primary prophylaxis) are conflicting, with insufficient evidence to use beta-blockers. In order to prevent first bleeding, there is strong evidence in patients with medium/large size oesophageal varices that either non-selective beta-blockers or banding ligation can be used. Banding is superior with respect to bleeding but mortality is similar. Non-selective beta-blockers should remain first line treatment being effective, cheap and without serious complications. In contrast banding ligation is more expensive, requires specialised staff, cannot prevent bleeding from portal hypertensive gastropathy and can cause iatrogenic bleeding. Patients with small varices, particularly if they have progressive liver disease also benefit from beta-blockers, but fewer studies confirm this therapeutic approach.

Which Factors Influence the Accuracy of Liver Stiffness Measurements by Transient Elastography (TE) and by Acoustic Radiation Force Impulse (ARFI) Elastography for Liver Fibrosis Evaluation? The Analysis of a Large International Cohort of Patients Simona Bota, Ioan Sporea, Markus Peck-Radosavljevic, Roxana Sirli, Hidetsugu Saito, Hirotoshi Ebinuma, Monica Platon Lupsor, Radu I. Badea, Mireen Friedrich-Rust, Christoph Sarrazin, Fabio Piscaglia, Sara Marinelli, Petra Salzl, Alina Popescu, Mirela Danila

Results: Variation coefficients for the balloon catheter were 0.07, 0.02, and 0.06 for HVPG, WHVP, and FHVP, respectively. Variation coefficients for the straight catheter were 0.17 (HVPG), 0.06 (WHVP), and 0.07 (FHVP), and significantly higher for HVPG and WHVP (p < 0.001) compared with the balloon catheter. When comparing the WHVP measurements with the portal venous pressure, the calculated intraclass correlation coefficient was 0.72 (p =0.004) using the balloon and 0.58 (p =0.011) using the straight catheter. Conclusion: Reproducibility and reliability of the HVPG measurement was higher using the balloon catheter, which should be the preferred procedure to measure HVPG. The significant greater variation coefficient of the straight catheter may become clinically relevant, if this method is used to perform repeated measurements during the management of cirrhotic patients.