The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis. The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis. In this mutual relationship, the liver acts as a second firewall towards potentially harmful substances translocated from the gut, and is, in turn, is implicated in the regulation of the barrier. Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage. In particular, in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment, diet and gut dysbiosis as the primary pathogenic trigger. In advanced liver disease, intestinal permeability is enhanced by portal hypertension. The clinical consequence is an increased bacterial translocation that further worsens liver damage. Furthermore, this pathogenic mechanism is implicated in most of liver cirrhosis complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma. After liver transplantation, the decrease in portal pressure should determine beneficial effects on the gut-liver axis, although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking. How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area, which deserves further attention.

The gut microbiota is involved in the maintenance of the homeostasis of the human body and its alterations are associated with the development of different pathological conditions. The liver is the organ most exposed to the influence of the gut microbiota, and recently important connections between the intestinal flora and hepatocellular carcinoma (HCC) have been described. In fact, HCC is commonly associated with liver cirrhosis and develops in a microenvironment where inflammation, immunological alterations, and cellular aberrations are dramatically evident. Prevention and diagnosis in the earliest stages are still the most effective weapons in fighting this tumor. Animal models show that the gut microbiota can be involved in the promotion and progression of HCC directly or through different pathogenic mechanisms. Recent data in humans have confirmed these preclinical findings, shedding new light on HCC pathogenesis. Limitations due to the different experimental design, the ethnic and hepatological setting make it difficult to compare the results and draw definitive conclusions, but these studies lay the foundations for a pathogenetic redefinition of HCC. Therefore, it is evident that the characterization of the gut microbiota and its modulation can have an enormous diagnostic, preventive, and therapeutic potential, especially in patients with early stage HCC.

Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.

Background The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has a tropism for the gastrointestinal tract and several studies have shown an alteration of the gut microbiota in hospitalized infected patients. However, long-term data on microbiota changes after recovery are lacking. Methods We enrolled 30 patients hospitalized for SARS‑CoV‑2-related pneumonia. Their gut microbiota was analyzed within 48 h from the admission and compared with (1) that of other patients admitted for suspected bacterial pneumonia (control group) (2) that obtained from the same subject 6 months after nasopharyngeal swab negativization. Results Gut microbiota alpha-diversity increased 6 months after the resolution of SARS-CoV-2 infection. Bacteroidetes relative abundance was higher (≈ 36.8%) in patients with SARS-CoV-2, and declined to 18.7% when SARS-CoV-2 infection resolved (p  =  0.004). Conversely, Firmicutes were prevalent (≈ 75%) in controls and in samples collected after SARS-CoV-2 infection resolution (p  =  0.001). Ruminococcaceae, Lachnospiraceae and Blautia increased after SARS-CoV-2 infection resolution, rebalancing the gut microbiota composition. Conclusion SARS-CoV-2 infection is associated with changes in the gut microbiome, which tend to be reversed in long-term period.