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Background The 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. Methods Ex 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. Results At 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. Conclusion LC-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.

Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.

The gut microbiota plays a key role in the progression of chronic liver disease and the development of hepatocellular carcinoma (HCC). However, findings on microbiota composition in such patients remain inconsistent, likely due to differences in disease aetiology and sample type. The mucosa-associated microbiota (MAM), residing in the intestinal mucin layer, more accurately reflects mucosal health than faecal microbiota, being more stable and less influenced by diet. This study aimed to characterise the ileal and sigmoid MAM in patients with chronic hepatitis C (CHC), liver cirrhosis (LC), and HCC. We performed DNA metabarcoding sequencing of mucosa samples collected from the ileum and sigmoid colon of patients at different stages of liver disease and healthy controls (HC). The predicted functions were analysed via phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) to infer metabolic pathways that can be expressed in the microbiome. Among 33 participants (20 HCV-related liver disease and 13 healthy controls), MAM α-diversity decreased significantly in advanced disease stages, particularly in LC and HCC, regardless of the metric applied (p ≤ 0.05). β-diversity analyses showed distinct microbial community structures across groups. Both ileal and sigmoid MAM were dominated by Bacteroidetes, Firmicutes, and Proteobacteria, with enrichment of Firmicutes_D, Proteobacteria, and Fusobacteria in LC and HCC. Several genera, including Bulleidia, Pantoea, Clostridium_Q, Rothia, and Streptococcus, were significantly increased in HCC, whereas beneficial taxa such as Akkermansia and Butyricimonas were depleted. Functional predictions indicated enrichment of degradative pathways (e.g., taurine, chitin derivatives, and carbohydrate metabolism) in LC and HCC. Our pilot study suggests that MAM alterations do not directly mirror liver disease progression but show distinct patterns associated with different stages. These associations, more evident in advanced disease, involve bacterial taxa linked to gut integrity, inflammation, and carcinogenesis. This exploratory work lays the groundwork for future studies to validate these findings and investigate their relevance to microbiome-based diagnostics and therapies in HCC.

Sclerosing mesenteritis (SM) is an idiopathic disorder affecting mesentery, characterized by fat necrosis, chronic inflammation and fibrosis. The clinical presentation varies from asymptomatic cases to acute abdomen. The diagnosis is suggested by imaging but can be definitely established only by biopsies. In this paper, we discuss ultrasonography-based management of SM.

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) represents a new inclusive definition of the whole spectrum of liver diseases associated to metabolic disorders. The main objective of this study was to compare patients with MAFLD and non-MAFLD with hepatocellular carcinoma (HCC) included in a nationally representative cohort.MethodsWe analysed 6882 consecutive patients with HCC enrolled from 2002 to 2019 by 23 Italian Liver Cancer centres to compare epidemiological and future trends in three subgroups: pure, single aetiology MAFLD (S-MAFLD); mixed aetiology MAFLD (metabolic and others, M-MAFLD); and non-MAFLD HCC.ResultsMAFLD was diagnosed in the majority of patients with HCC (68.4%). The proportion of both total MAFLD and S-MAFLD HCC significantly increased over time (from 50.4% and 3.6% in 2002–2003, to 77.3% and 28.9% in 2018–2019, respectively, p<0.001). In Italy S-MAFLD HCC is expected to overcome M-MAFLD HCC in about 6 years. Patients with S-MAFLD HCC were older, more frequently men and less frequently cirrhotic with clinically relevant portal hypertension and a surveillance-related diagnosis. They had more frequently large tumours and extrahepatic metastases. After weighting, and compared with patients with non-MAFLD, S-MAFLD and M-MAFLD HCC showed a significantly lower overall (p=0.026, p=0.004) and HCC-related (p<0.001, for both) risk of death. Patients with S-MAFLD HCC showed a significantly higher risk of non-HCC-related death (p=0.006).ConclusionsThe prevalence of MAFLD HCC in Italy is rapidly increasing to cover the majority of patients with HCC. Despite a less favourable cancer stage at diagnosis, patients with MAFLD HCC have a lower risk of HCC-related death, suggesting reduced cancer aggressiveness.

Background Laparoscopic microwave ablation (LMWA) has yet to gain a specific place in treatment guidelines for early hepatocellular carcinoma (HCC). This study compared the outcomes of LMWA and trans-arterial chemoembolization (TACE) for early non-resectable patients with HCC, taking percutaneous radiofrequency ablation (PRFA) as the reference treatment. Methods A retrospective multicenter observational study was conducted, enrolling non-transplantable, non-resectable patients who had early HCC treated with LMWA ( n = 658) from Padua and Milan centers, and with PRFA ( n = 844), and TACE ( n = 425) from the ITA.LI.CA multicenter database. The matching-adjusted indirect comparison (MAIC) method was used to obtain weighted LMWA and TACE populations similar to the reference PRFA population. Results Laparoscopic ablation showed an excellent safety profile, and MAIC-weighted early postoperative deaths were comparable among the groups. The MAIC-weighted overall survival was similar between the LMWA (1-, 3-, and 5 year survival of 91.0 %, 67.9 %, 47.0 %, respectively) and PRFA (1-, 3- and 5 year survivals of 90.0 %, 64.7 %, 46.6 %, respectively) groups ( p = 0.678) and significantly better for the LMWA group than for the TACE group (1-, 3- and 5 year survivals of 84.7 %, 48.8 %, 33.6 %, respectively) ( p < 0.001). Weighted multivariate overall survival analysis and competing risk/subgroup analyses confirmed the non-inferiority of LMWA to PRFA and its superiority to TACE. The LMWA- and PRFA-treated patients had a significantly lower risk of HCC-related death ( p = 0.004) than the TACE-treated patients ( p = 0.001). Conversely, the groups did not differ significantly in terms of non-HCC-related deaths. Conclusions The non-inferiority of LMWA to PRFA, its superiority to TACE, and its applicability to a wide range of presentations with few contraindications support its inclusion among radical therapies for treating early-HCC patients.

Background In vitro, vitamin B12 acts as a natural inhibitor of hepatitis C virus (HCV) replication. Objective To assess the effect of vitamin B12 on virological response in patients with chronic HCV hepatitis naïve to antiviral therapy. Methods Ninety-four patients with chronic HCV hepatitis were randomly assigned to receive pegylated interferon α plus ribavirin (standard-of-care; SOC) or SOC plus vitamin B12 (SOC+B12). Viral response—namely, undetectable serum HCV-RNA, was evaluated 4 weeks after starting treatment (rapid viral response), 12 weeks after starting treatment (complete early viral response) and 24 or 48 weeks after starting treatment (end-of-treatment viral response) and 24 weeks after completing treatment (sustained viral response (SVR)). Genotyping for the interleukin (IL)-28B polymorphism was performed a posteriori in a subset (42/64) of HCV genotype 1 carriers. Results Overall, rapid viral response did not differ between the two groups, whereas the rates of complete early viral response (p=0.03), end-of-treatment viral response (p=0.03) and SVR (p=0.001) were significantly higher in SOC+B12 patients than in SOC patients. In SOC+B12 patients, the SVR rate was also significantly higher in carriers of a difficult-to-treat genotype (p=0.002) and in patients with a high baseline viral load (p=0.002). Distribution of genotype IL-28B did not differ between the two groups. At multivariate analysis, only easy-to-treat HCV genotypes (OR=9.00; 95% CI 2.5 to 37.5; p=0.001) and vitamin B12 supplementation (OR=6.9; 95% CI 2.0 to 23.6; p=0.002) were independently associated with SVR. Conclusion Vitamin B12 supplementation significantly improves SVR rates in HCV-infected patients naïve to antiviral therapy.