BACKGROUND AND AIMS: The supposedly lower sensitivity of the faecal immunochemical test (FIT) for proximal colon tumours is an open question. We compared the observed annual (1997-2017) tumour site-specific incidence rat...BACKGROUND AND AIMS: The supposedly lower sensitivity of the faecal immunochemical test (FIT) for proximal colon tumours is an open question. We compared the observed annual (1997-2017) tumour site-specific incidence rates of colorectal cancer (CRC) in the target population (over 1,300,000 aged 50-69 years) of an Italian regional FIT screening programme with the rates that would be expected in the absence of screening. METHODS: For proximal colon cancer, the expected rates were estimated with an age-period model in both sexes combined, showing an increasing trend. For distal colon cancer and rectal cancer, the best fit to the observed rates was provided by an age-period-cohort model (men) and an age-period model (women), both showing a stable trend. RESULTS: In the 11th and 12th full years of screening, the decrease in incidence was of the same magnitude for proximal colon cancer (rate ratio: 0.55 and 0.49 among men; 0.63 and 0.57 among women) and distal colon cancer (0.50 and 0.50; 0.60 and 0.61). The decrease was less pronounced for rectal cancer. CONCLUSION: Thanks to the increase in the modelled expected incidence of proximal colon cancer alone, the impact of FIT screening on the incidence of CRC was similar between colonic segments.
Genetic and familial susceptibility accounts for 10% of pancreatic ductal adenocarcinoma (PDAC) cases and represents a small but relevant subgroup in which early detection may meaningfully affect outcomes. Pathogenic ger...Genetic and familial susceptibility accounts for 10% of pancreatic ductal adenocarcinoma (PDAC) cases and represents a small but relevant subgroup in which early detection may meaningfully affect outcomes. Pathogenic germline variants (PGVs) in susceptibility genes, such as BRCA2/ATM/CDKN2A/STK11/PALB2/TP53, as well as mismatch repair genes, confer a substantially higher lifetime risk, while families fulfilling the criteria for familial pancreatic cancer (FPC) exhibit disease clustering in the absence of an identifiable PGV. Over the past two decades, surveillance strategies for high-risk individuals (HRIs) have evolved from exploratory registries to structured clinical programs, generating expanding evidence with tangible clinical implications. Data from the international CAPS (Cancer of the Pancreas Screening) consortium, the Dutch nationwide surveillance program, and the IRFARPC (Italian Registry of Families at Risk for Pancreatic Cancer) consistently demonstrate a stage shift toward earlier, resectable disease and improved survival among cancers detected under surveillance. However, uncertainties remain regarding the magnitude of benefit, eligibility criteria, surveillance start age, cost-effectiveness, and the risk of overdiagnosis. This review critically appraises current evidence, focusing on the Italian and European experience, evaluates the pros and cons of HRIs surveillance, and proposes updated criteria and considerations for a structured, registry-based national program aligned with new evidence.
BACKGROUND: Treat-to-target strategies in inflammatory bowel disease (IBD) rely on repeated objective assessments, leading to frequent colonoscopy for therapeutic decision-making. Although effective, endoscopic monitorin...BACKGROUND: Treat-to-target strategies in inflammatory bowel disease (IBD) rely on repeated objective assessments, leading to frequent colonoscopy for therapeutic decision-making. Although effective, endoscopic monitoring is resource-intensive and may not be necessary in all stable patients. AIMS: To evaluate the environmental and economic impact of intestinal ultrasound (IUS) compared with colonoscopy for therapeutic monitoring in IBD. METHODS: In this single-center retrospective cohort (2022-2024), 200 adults with IBD undergoing both IUS and colonoscopy were analyzed. The functional unit was one monitoring episode. For each modality, we quantified carbon dioxide equivalent emissions (CO₂e), energy use (kWh), and disposable waste (g) within defined system boundaries. Procedure cost was assessed as a secondary outcome. A patient-level model projected cumulative impact across ten monitoring cycles, comparing an IUS + fecal calprotectin (FCP >250 μg/g) strategy with colonoscopy-for-all. RESULTS: Per procedure, colonoscopy required +0.91 kWh, emitted +2.9 kg CO₂e, and generated +212 g disposables versus IUS (all p<0.001). IUS reduced energy use by ∼95%, CO₂e by ∼100-fold, and disposables by ∼85%. Over ten cycles, an IUS-first strategy reduced cumulative CO₂e emissions and costs by ∼40% (both p<0.05). CONCLUSIONS: IUS substantially lowers environmental and economic burden compared with colonoscopy while supporting timely therapeutic decisions. An IUS + FCP-first approach represents a pragmatic, sustainable monitoring strategy in IBD.
BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICIs) improve cancer outcomes but can lead to immune-mediated hepatotoxicity (IMH). Real-world data on severe IMH remain limited. This study aimed to identify risk facto...BACKGROUND AND AIMS: Immune checkpoint inhibitors (ICIs) improve cancer outcomes but can lead to immune-mediated hepatotoxicity (IMH). Real-world data on severe IMH remain limited. This study aimed to identify risk factors and evaluate clinical outcomes, including the safety of ICIs rechallenge. METHODS: This retrospective dual-center study included patients who developed IMH after ICIs therapy at two high-volume hospitals in China. Univariable and multivariable logistic regression were used to identify independent risk factors. The timing of onset was assessed by treatment cycles, and outcomes of patients who underwent rechallenge were analyzed. RESULTS: Among 408 patients with IMH, 175 had severe disease. Multivariable analysis identified hepatitis B virus (HBV) infection (OR 1.99, 95% CI 1.16-3.40), liver malignancy (OR 1.89, 95% CI 1.13-3.18), cholelithiasis (OR 2.28, 95% CI 1.41-3.71), and elevated lactate dehydrogenase (LDH) (OR 1.87, 95% CI 1.04-3.39) as independent risk factors. IMH occurred mainly within the first four ICIs cycles, with significantly earlier onset in HBV-positive patients (median 2 vs. 3 cycles, P = 0.038). Among 130 patients with grade 3 IMH, 94.6% recovered. ICIs rechallenge was performed in 65 patients after adequate recovery of liver function; 61/65 (93.8%) were able to continue ICIs, and recurrent hepatotoxicity was generally mild. CONCLUSION: Severe IMH was independently associated with HBV infection, liver malignancy, cholelithiasis, and elevated LDH. Grade 3 IMH was largely reversible and, in selected patients with adequate liver function recovery and without severe systemic irAEs, could allow cautious and individualized ICIs rechallenge.
Primary sclerosing cholangitis (PSC) is an immune-mediated fibro-obliterative disease of the biliary tree which culminates in biliary cirrhosis and decompensated liver failure. Increasing in incidence, PSC comprises a gr...Primary sclerosing cholangitis (PSC) is an immune-mediated fibro-obliterative disease of the biliary tree which culminates in biliary cirrhosis and decompensated liver failure. Increasing in incidence, PSC comprises a growing indication for liver transplantation (LT) with LT remaining the only proven life-prolonging therapy in patients with PSC. Recurrence of PSC (rPSC) after LT is however poorly understood and poses a further challenge due to heterogeneity in diagnostic criteria and proposed negative associations with graft failure and overall survival. This review explores the current literature surrounding rPSC including diagnosis, epidemiology, therapeutic options and patient outcomes. We discuss the challenges in the management of rPSC. Given the scarcity of literature and frequency of re-transplantation for rPSC, further clinical investigation is necessary to identify risk factors and effective therapies in this cohort of patients.
BACKGROUND: Liver cirrhosis is a complex disease characterized by chronic inflammation and immune dysregulation, which leads to the progressive development of liver fibrosis. Glycosylation, as a critical post-translation...BACKGROUND: Liver cirrhosis is a complex disease characterized by chronic inflammation and immune dysregulation, which leads to the progressive development of liver fibrosis. Glycosylation, as a critical post-translational modification, plays a pivotal role in regulating immune cell functions. However, its specific role in T/NK cells during the progression of cirrhosis remains insufficiently understood. METHODS: This study integrates single-cell transcriptomics and glycosylation profiling to investigate changes in glycosylation-related gene expression and cellular interactions in T/NK cells from cirrhotic versus healthy liver tissues. We systematically evaluated immune cell composition, glycosylation alterations, and intercellular communication networks to elucidate the mechanisms underlying immune dysregulation in cirrhosis. RESULTS: Significant alterations in glycosylation patterns and gene expression profiles were observed in T/NK cells from cirrhotic livers. These changes were associated with shifts in immune cell subsets and enhanced cell-cell interactions, suggesting that glycosylation modifications may play a role in modulating immune responses. CONCLUSIONS: Our findings underscore the importance of glycosylation dynamics in the functional regulation of T/NK cells during liver cirrhosis. Targeting glycosylation pathways may offer novel therapeutic strategies to address immune imbalance and fibrosis in cirrhosis.
Patients with cirrhosis are not spontaneously anticoagulated. Patients with cirrhosis are at risk of developing venous thromboembolism and atrial fibrillation. Anticoagulation does not independently increase the risk of...Patients with cirrhosis are not spontaneously anticoagulated. Patients with cirrhosis are at risk of developing venous thromboembolism and atrial fibrillation. Anticoagulation does not independently increase the risk of bleeding related to portal hypertension; or the mortality and morbidity related to bleeding. VTE prophylaxis should be considered in hospitalized patients with cirrhosis. Deep vein thrombosis and pulmonary embolism should be treated with anticoagulation. Portal vein thrombosis is a marker for the severity of liver disease but likely not an aggravating factor. Current data suggest that anticoagulation therapy is beneficial in patients with cirrhosis and portal hypertension with or without portal vein thrombosis. Direct oral anticoagulants have taken a predominant place among anticoagulants in patients with cirrhosis in the absence of decompensation.
BACKGROUND: Obstructive colon cancer (OCC) is at poor prognosis, and the high morbidity of emergency resection frequently delays or precludes adjuvant chemotherapy. A strategy with first step diverting stoma - neoadjuvan...BACKGROUND: Obstructive colon cancer (OCC) is at poor prognosis, and the high morbidity of emergency resection frequently delays or precludes adjuvant chemotherapy. A strategy with first step diverting stoma - neoadjuvant chemotherapy (NAC) - colectomy in non-metastatic OCC may represent an alternative to the conventional strategy of stoma followed by colectomy. METHOD: COnCERTO is a multicenter, open-label, randomized (1:1), phase III trial evaluating NAC followed by colectomy ± adjuvant chemotherapy versus standard-of-care colectomy ± adjuvant chemotherapy in adults with resectable non-metastatic MSS OCC first treated by a defunctionning stoma. Two hundred and thirty-two will be randomized across 37 French centers. The primary endpoint is the rate of complete curative therapeutic sequence combining the resection of the primary and the administration of scheduled NAC and/ or adjuvant chemotherapy. Secondary endpoints include the tolerance and compliance of NAC and/ or adjuvant chemotherapy (SRAE ≥ grade 3, CTCAE v5.0), quality and completeness of the surgical excision, 90 days postoperative morbidity, health-related quality of life, OS and DFS at 3 years and survival without stoma at 3 years. Randomization started in May 2024. DISCUSSION: COnCERTO will determine whether a NAC approach can be pursued safely and effectively in localized OCC and translate into a better cancer control and quality of life improvement. REGISTRATION NUMBER: ClinicalTrials.gov NCT06107920.
BACKGROUND: Minimal hepatic encephalopathy (MHE) is a neuropsychiatric syndrome that significantly affects quality of life. It is associated with neural activity changes, reflected by the amplitude of low-frequency fluct...BACKGROUND: Minimal hepatic encephalopathy (MHE) is a neuropsychiatric syndrome that significantly affects quality of life. It is associated with neural activity changes, reflected by the amplitude of low-frequency fluctuation (ALFF) in resting-state functional magnetic resonance imaging (rs-fMRI). Zinc deficiency compromises cognition; however, its relationship with the neural activity changes in MHE remains unclear. AIMS: To investigate blood zinc variations in MHE and their associations with ALFF. METHODS: Blood zinc levels were compared in 150 patients with cirrhosis. Among them, 49 underwent rs-fMRI to evaluate associations between zinc levels and ALFF, after adjusting for confounders. RESULTS: Blood zinc levels were significantly lower in patients with MHE than in those with no hepatic encephalopathy (4.63 vs. 5.06 mg/L; P = 0.022). MHE prevalence was higher in females than in males (35.2% vs. 19.0%; P = 0.025). ALFFs in the bilateral angular gyrus and precuneus were positively correlated with blood zinc levels, whereas those in the bilateral fusiform gyrus were negatively correlated (P < 0.05 and P < 0.05, respectively). CONCLUSIONS: Low blood zinc levels in patients with MHE are associated with altered neural activity in the bilateral angular gyrus, precuneus, and bilateral fusiform gyrus, representing a neural basis for cognitive impairment in MHE.
Functional dyspepsia (FD) is a prevalent disorder of gut-brain interaction. Commonly, meals may exacerbate FD symptoms like postprandial fullness, early satiation, epigastric pain, and nausea. We narratively synthesize m...Functional dyspepsia (FD) is a prevalent disorder of gut-brain interaction. Commonly, meals may exacerbate FD symptoms like postprandial fullness, early satiation, epigastric pain, and nausea. We narratively synthesize meta-analyses, randomized trials, and observational evidence to outline mechanism-based dietary and nutraceutical options. Evidence favors small, regular, lower-fat meals and adjusting texture/osmolarity to minimize gastric distension. In selected phenotypes-particularly postprandial distress with bloating-a brief, dietitian-supervised low-FODMAP trial with staged reintroduction can define personal thresholds. Among nutraceuticals, peppermint-caraway, ginger, STW-5, curcumin, and selected probiotics show benefit, with melatonin and barrier-forming agents promising in subsets, while safety remains product-specific.
Balsano C, Alisi A, Burra P
… +13 more, Calvaruso V, Cammà C, Campagner A, Donatelli P, Germani G, Gerussi A, Giuffrè M, Lleo A, Panebianco V, Persico M, Pugliese N, Rossi S, Artificial Intelligence Committee
Artificial Intelligence (AI) is transforming medicine, providing unprecedented opportunities to enhance diagnosis, prognosis, and treatment across all areas of hepatology. This Position Paper by the Italian Association f...Artificial Intelligence (AI) is transforming medicine, providing unprecedented opportunities to enhance diagnosis, prognosis, and treatment across all areas of hepatology. This Position Paper by the Italian Association for the Study of the Liver (AISF) offers a comprehensive overview of the current and emerging roles of AI in liver diseases, highlighting both its promise and its limitations. The document critically examines methodological, ethical, and educational challenges associated with AI integration in clinical and research settings, and reviews key applications in MASLD/MASH, alcohol-related liver disease, autoimmune and cholestatic liver diseases, viral hepatitis, drug-induced liver injury, hepatocellular carcinoma, cholangiocarcinoma, and liver transplantation. Particular emphasis is placed on data quality, algorithmic fairness, explainability, and reproducibility, as well as on the necessity of robust external validation and adherence to international reporting standards (TRIPOD-AI, CONSORT-AI, DECIDE-AI, CHAMAI and others). The AISF advocates a responsible and evidence-based adoption of AI through multidisciplinary collaboration, professional education, and patient engagement. This Position Paper outlines a national roadmap to align AI innovation with ethics, transparency, and equity, ensuring that AI becomes a genuine ally of hepatology and patient-centered care.