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BackgroundThe evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model.MethodsEx vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting.ResultsAt baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment.ConclusionLC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D.

The presence of significant fibrosis is an indicator for liver disease staging and prognosis.The aim of the study was to determine reproducibility of real-time shear wave elastography using a hepatic biopsy as the reference standard to identify patients with chronic liver disease. Forty patients with chronic liver disease and 12 normal subjects received shear wave elastography performed by skilled operators. Interoperator reproducibility was studied in 29 patients. Fibrosis was evaluated using the Metavir score. The median and range shear wave elastography values in chronic liver disease subjects were 6.15 kPa and 3.14–16.7 kPa and were 4.49 kPa and 2.92–7.32 kPa in normal subjects, respectively. With respect to fibrosis detected by liver biopsy, shear wave elastography did not change significantly between F0 and F1 (p = 0.334), F1 and F2 (p = 0.611), or F3 and F4 (0.327); a significant difference was observed between the F0-F2 and F3-F4 groups (p = 0.002). SWE also correlated with inflammatory activity (Rs = 0.443, p = 0.0023) and ALT levels (Rs = 0.287, p = 0.0804). Age, sex and body mass index did not affect shear wave elastography measurements. Using receiver operator characteristic curves, two threshold values for shear wave elastography were identified: 5.62 kPa for patients with fibrosis (≥F2; sensitivity 80%, specificity 69.4%, and accuracy 77%) and 7.04 kPa for patients with severe fibrosis (≥F3; sensitivity 88.9%, specificity 81%, and accuracy 89%). Overall interobserver agreement was excellent and was analysed using an interclass correlation coefficient (0.94; CI 0.87–0.97).This study shows that shear wave elastography executed by skilled operators can be performed on almost all chronic liver disease patients with high reproducibility. It is not influenced by age, sex or body mass index, identifies severely fibrotic patients and is also related to inflammatory activity.

The prevalence of metabolic disorders, such as type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD), which are common risk factors for cardiovascular disease (CVD), has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.

Vitamin B12 supplementation significantly improves SVR rates in HCV-infected patients naïve to antiviral therapy.

The antirejection drug tacrolimus (FK506) has been reported to impair intestinal permeability in an early stage after orthotopic liver transplantation (OLT), and cyclosporine (CsA) has shown a similar effect in animals. We studied the chronic effect of FK506 and CsA on gastroduodenal and intestinal permeability and on blood endotoxin levels in patients 2 to 3 years after OLT. Thirty-two OLT patients (22 men and 10 women; mean age, 44.8 ؎ 7.1) who had received CsA (n ‫؍‬ 19) or FK506 (n ‫؍‬ 13) and 10 healthy volunteers (6 male and 4 female, mean age 41.7 ؎ 5.4) were assessed for gastroduodenal permeability by recovery in urine of sucrose after oral administration and for intestinal permeability by recovery in urine after oral loads of rhamnose and lactulose, which evaluate the intracellular and paracellular routes, respectively. In all subjects, plasma levels of endotoxins also were assessed. Gastroduodenal permeability was similar in patients and controls (0.03 ؎ 0.003 versus 0.04 ؎ 0.01%, P ‫؍‬ NS). In regard to intestinal permeability, passage through the intracellular route was significantly reduced in OLT patients compared with controls (1.13 ؎ 0.06 versus 2.74 ؎ 0.17%, P < .01), but paracellular permeability was unchanged (0.14 ؎ 0.007 versus 0.13 ؎ 0.01%, P ‫؍‬ NS). Serum endotoxin levels were similar in all subjects. We conclude that chronic administration of FK506 or CsA induces a clinically irrelevant, selective dysfunction of monosaccharide absorption, but does not affect gastroduodenal or intestinal permeability. (Liver Transpl 2003;9:484-488.) D uring the last decade, an increasing number of subjects underwent orthotopic liver transplantation (OLT). 1 In Europe, the average survival rate 1 year after OLT currently is over 80%, and morbidity and mortality rates after transplantation are receiving increasing attention. 1 Infections, neoplasms and autoimmune disease, and a higher risk of hypertension and lipid abnormalities usually are observed after OLT, and all can negatively affect the outcome of the transplant. 2,3 Most of the metabolic alterations observed after OLT likely are associated with the use of immunosuppressive drugs, and various side effects have been reported during chronic therapy with cyclosporine (CsA) and tacrolimus (FK506). 4,5 During immunosuppressive and cytotoxic therapy, the intestinal epithelium can lose its barrier function. 6,7 This function can be evaluated in vivo by tests based on permeability of small intestine to sugar probes such as lactulose (Lacl) and rhamnose (L-Rh), administered orally and recovered in urine. 8 The ratio between urinary Lacl and L-Rh has been used to evaluate altered intestinal permeability in conditions such as immunodepression, 9,10 viral gastroenteritis, 11,12 coeliac disease, 13 and Crohn's disease. 14 In these conditions, the increased permeation of macromolecules through the intestinal wall takes place generally through the paracellular pathway and may be associated with high levels of plasmatic endotoxins. 15,16 FK506 has been reported to i...

Background and aims In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MaVI) limits treatment options and decreases survival. Detailed data on the relationship between MaVI extension and patients' characteristics, and its impact on patients' outcome are limited. We evaluated the prevalence and extension of MaVI in a large cohort of consecutive HCC patients, analysing its association with liver disease and tumour characteristics, as well as with treatments performed and patients' survival. Methods We analysed data of 4774 patients diagnosed with HCC recorded in the Italian Liver Cancer (ITA.LI.CA) database (2008‐2018). Recursive partition analysis (RPA) was performed to evaluate interactions between MaVI, clinical variables and treatment, exploring the inter‐relationship determining overall survival. Results MaVI prevalence was 11.1%, and median survival of these patients was 6.0 months (95% CI, 5.1‐7.1). MaVI was associated with younger age at diagnosis, presence of symptoms, worse Performance Status (PS) and liver function, high alphafetoprotein levels and large HCCs. MaVI extension was associated with worse PS, ascites and greater impairment in liver function. RPA identified patients' categories with different treatment indications and survival, ranging from 2.4 months in those with PS > 1 and ascites, regardless of MaVI extension (receiving best supportive care in 90.3% of cases), to 14.1 months in patients with PS 0‐1, no ascites and Vp1‐Vp2 MaVI (treated with surgery in 19.1% of cases). Conclusions MaVI presence and extension, together with PS and ascites, significantly affect patients' survival and treatment selection. The decision tree based on these parameters may help assess patients' prognosis and inform therapeutic decisions.

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