Resmetirom, a thyroid hormone receptor-β agonist, has been approved for non-cirrhotic metabolic dysfunction–associated steatohepatitis (MASH) with moderate-to-advanced fibrosis (F2-F3). In clinical practice, treatment allocation will primarily rely on non-invasive tests (NITs). We aimed to quantify, in a real-world MASLD cohort, the proportion and clinical characteristics of patients deemed eligible for Resmetirom according to the AASLD Practice Guidance and Noureddin Expert Panel frameworks.We retrospectively analysed consecutive adults with MASLD evaluated at four Italian tertiary centres. Demographic, clinical, laboratory, vibration-controlled transient elastography (VCTE) were retrieved from electronic records; liver biopsy data were available for 175 patients. Eligibility was defined according to NIT-based criteria mirroring the AASLD framework (VCTE 8-15 kPa, without clinical or ultrasound evidence of cirrhosis or portal hypertension) and the Noureddin framework (VCTE 10-19.9 kPa, platelets ≥140 × 10⁹/L, no evidence of cirrhosis). We assessed eligibility proportions, concordance between frameworks, and independent correlates of eligibility. In the biopsy subset, we examined how histologic F2-F3 patients were classified.The cohort included 908 consecutive patients (57% males), with a median age of 62 years and median BMI of 29.4 kg/m²; 48% had obesity, 47% were overweight, and 36% had type 2 diabetes (T2D). Overall, 22.6% (205/908) of patients were AASLD-eligible and 12.9% (117/908) Noureddin-eligible, with a crude agreement of 84.3% and Cohen’s κ 0.468. In multivariable analysis, older age, higher BMI, and T2D were independently associated with eligibility in both frameworks, while higher FIB-4 was inversely associated with Noureddin eligibility. In the biopsy subset, both frameworks identified only a fraction of histologic F2-F3 cases: 52.1% with AASLD and 32.9% with Noureddin criteria, while the remaining 47.9% and 67.1%, respectively, were not eligible, mostly due to VCTE values below threshold. The AASLD and Noureddin frameworks identify overlapping but non-interchangeable populations. The AASLD criteria are broader, while Noureddin’s are more selective but risk excluding many F2–F3 patients. Integrated clinical–NIT algorithms may better identify MASLD patients most likely to benefit from resmetirom.

INTRODUCTION:Hepatitis C virus (HCV) infection represents a significant global health burden, particularly due to its extrahepatic immune-mediated manifestations, such as mixed cryoglobulinemia, associated vasculitis (CryoVas), and non-Hodgkin B-cell lymphoma (B-NHL), which pose significant challenges. The advent of direct-acting antiviral (DAA) has changed the therapeutic landscape for HCV-related complications. AREAS COVERED:This review explores the evolving epidemiology and management of HCV extrahepatic manifestation and lymphoproliferative disorders in the era of DAAs. It examines the efficacy of DAAs in controlling CryoVas and their complex role in HCV-related B-cell lymphoma. The literature search included studies on the immunological dynamics between HCV, CryoVas, and lymphoma, focusing on the impact of sustained virological response (SVR) on immune dysregulation, relapse risk, refractory disease, and patient stratification based on risk profiles. EXPERT OPINION:DAAs have significantly improved the management of HCV-related CryoVas and autoimmune manifestations, but remain a challenge in refractory cases and the risk of lymphoma. Future strategies should focus on refining risk stratification and integrating new therapeutic approaches to better address immune dysregulation and associated complications.

Background Liver diseases are common in patients with inflammatory bowel disease (IBD). Little is known about how specialists perceive and manage liver enzyme abnormalities. This study investigates the current practice and educational needs of IBD specialists in the management of liver enzyme abnormalities. Methods A 22-question web-based survey was distributed to members of the Italian Group for the study of IBD, covering their demographics, workplace features, and approaches to managing liver enzyme abnormalities in IBD patients. Results The survey was completed by 205/439 (46.7%) respondents. The majority of respondents were over 45 years old (38.5%) and worked in Northern Italy (61%). Most were gastroenterologists (86%) practicing in public hospitals (45%), with 21.5% having a defined referral pathway to a dedicated liver unit for IBD patients. Ninety-seven percent of physicians reported regular monitoring of transaminases, while 88% also monitored gamma-glutamyl transpeptidase and 76% alkaline phosphatase (ALP). In cases of abnormal enzyme levels, over 70% reported ordering additional diagnostic tests independently, with notable heterogeneity in the thresholds used to trigger further investigation. The conditions most frequently suspected in cases of mild transaminase elevations were metabolic dysfunction-associated steatotic liver disease (71%) and drug-induced liver injury (17%). A significant proportion of physicians (57%) considered their training in managing liver enzyme abnormalities adequate but acknowledged the need for further educational opportunities. The main barrier identified was the lack of specific guidelines and actionable flowcharts (62%). Conclusion This survey reveals heterogeneity in monitoring and management of liver enzyme abnormalities among IBD specialists. Most physicians recognize the need for improved training and specific guidelines.

The hepatitis C virus (HCV) is a major cause of liver-related morbidity and mortality, and a major risk factor of hepatocellular carcinoma (HCC) around the world. Early detection, continued prevention of transmission, and antiviral treatment of chronically infected persons are the pillars to decrease incidence and mortality of HCV. The widespread access to safe and effective direct acting anti-viral agents (DAA) has allowed the elimination of the infection possible in almost all treated patients, thus leading to a significant reduction of liver-related and overall mortality due to HCV in the cured population. Treatment of HCV does not completely eradicate HCC risk in populations with advanced liver disease and those with cofactors known to promote liver carcinogenesis such as diabetes, obesity, and excessive alcohol consumption. Molecular-based biomarkers are expected to overcome the limits of liver disease severity, thus improving the identification of screening candidates. The implementation of risk-stratified surveillance programs coupled with the identification of biomarkers to predict HCC in HCV cured patents is deemed necessary for implementing the cost-effective management of these patients.

Background and aims: Hereditary colorectal cancer syndromes (HCCS), including familial adenomatous polyposis (FAP) and Lynch syndrome (LS), are the two most important high-risk conditions for colorectal cancer (CRC). Inflammatory bowel disease (IBD) increases the risk by two to six times compared with that in the general population. The intersection of these two conditions has rarely been documented in literature. We aimed to summarize the prevalence, pathogenesis, and current evidence-based management of IBD and HCCS and the underlying molecular mechanisms of accelerated carcinogenesis due to combined inflammation and genetic predisposition. Methods: PubMed and Scopus were searched until June 2024 to identify relevant studies investigating the epidemiology, pathogenesis, and management of IBD and coexisting hereditary CRC syndromes. Results: Co-occurrence of IBD and hereditary CRC syndromes is exceptionally uncommon. Individuals with LS and IBD tend to develop CRC at a younger age than those without IBD, with patients with ulcerative colitis facing particularly elevated risks. The interaction between mismatch deficiency and chronic inflammation requires further investigation.

Background: Artificial intelligence (AI)-based chatbots have shown promise in providing counseling to patients with metabolic dysfunction-associated steatotic liver disease (MASLD). While ChatGPT3.5 has demonstrated the ability to comprehensively answer MASLD-related questions in English, its accuracy remains suboptimal. Whether language influences these results is unclear. This study aims to assess ChatGPT’s performance as a counseling tool for Italian MASLD patients. Methods: Thirteen Italian experts rated the accuracy, completeness and comprehensibility of ChatGPT3.5 in answering 15 MASLD-related questions in Italian using a six-point accuracy, three-point completeness and three-point comprehensibility Likert’s scale. Results: Mean scores for accuracy, completeness and comprehensibility were 4.57 ± 0.42, 2.14 ± 0.31 and 2.91 ± 0.07, respectively. The physical activity domain achieved the highest mean scores for accuracy and completeness, whereas the specialist referral domain achieved the lowest. Overall, Fleiss’s coefficient of concordance for accuracy, completeness and comprehensibility across all 15 questions was 0.016, 0.075 and −0.010, respectively. Age and academic role of the evaluators did not influence the scores. The results were not significantly different from our previous study focusing on English. Conclusion: Language does not appear to affect ChatGPT’s ability to provide comprehensible and complete counseling to MASLD patients, but accuracy remains suboptimal in certain domains.

Porto-sinusoidal vascular disorder (PSVD) encompasses a group of vascular disorders characterized by lesions of the portal venules and sinusoids with clinical manifestations ranging from non-specific abnormalities in serum liver enzymes to clinically overt portal hypertension and related complications. Several reports have documented cases of PSVD in patients with systemic autoimmune conditions, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. It is of note that these diseases share specific pathophysiological features with PSVD, including endothelial dysfunction, vascular inflammation, and molecular signatures. This narrative review aims to summarize the current knowledge on the association between PSVD and systemic autoimmune diseases, emphasizing the importance of promptly recognizing this condition in the rheumatological practice, and highlighting the key aspects where further research is necessary from both pathogenic and clinical perspectives.

Aims: Lumen-apposing metal stents (LAMSs) in ultrasonography-guided gallbladder drainage (EUS-GBD) have become increasingly important for high-risk surgical patients. Our study aims to evaluate the technical and clinical success, safety, and feasibility of endoscopic ultrasonography-guided gallbladder drainage using a new dedicated LAMS. Methods: This is a retrospective multicenter study that included all consecutive patients not suitable for surgery who were referred to a tertiary center for EUS-GBD using a new dedicated electrocautery LAMS for acute cholecystitis at eight different centers. Results: Our study included 54 patients with a mean age of 76.48 years (standard deviation: 12.6 years). Out of the 54 endoscopic gallbladder drainages performed, 24 (44.4%) were cholecysto-gastrostomy, and 30 (55.4%) were cholecysto-duodenostomy. The technical success of LAMS placement was 100%, and clinical success was achieved in 23 out of 30 patients (76.67%). Adverse events were observed in two patients (5.6%). Patients were discharged after a median of 5 days post-stenting. Conclusions: EUS-GBD represents a valuable option for high-surgical-risk patients with acute cholecystitis. This new dedicated LAMS has demonstrated a high rate of technical and clinical success, along with a high level of safety.

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug–drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

Alessandro Gubbiotti: NO financial relationship with a commercial interest | Marco Spadaccini: NO financial relationship with a commercial interest | Roberta Maselli: YES financial relationship with a commercial interest;fujifilm :Consulting;erbe medical :Consulting;boston scientific :Consulting | Andrea Anderloni: YES financial relationship with a commercial interest;boston scientific:Consulting;olympus:Consulting;medtronic:Consulting | Alessandro Fugazza: YES financial relationship with a commercial interest;Boston Scientific:Consulting;Olympus:Consulting | Silvia Carrara: YES financial relationship with a commercial interest;Olympus:Speaking and Teaching | Elisa Chiara Ferrara: No Answer. | Piera Alessia Galtieri: NO financial relationship with a commercial interest | Gaia Pellegatta: No Answer. | Vincenzo Craviotto: NO financial relationship with a commercial interest | Leonardo Da Rio: NO financial relationship with a commercial interest | Ludovico Alfarone: NO financial relationship with a commercial interest | Giulia Migliorisi: NO financial relationship with a commercial interest | Benedetta Masoni: NO financial relationship with a commercial interest | Luca Brandaleone: NO financial relationship with a commercial interest | Peter Bertoli: NO financial relationship with a commercial interest | Valeria Poletti: NO financial relationship with a commercial interest | Silvia Ferretti: NO financial relationship with a commercial interest | Davide Polverini: NO financial relationship with a commercial interest | Giacomo Marcozzi: NO financial relationship with a commercial interest | Gianluca Franchellucci: NO financial relationship with a commercial interest | Maria Terrin: NO financial relationship with a commercial interest | Alessandro De Marco: NO financial relationship with a commercial interest | Elisabetta Mastrorocco: NO financial relationship with a commercial interest | Cesare Hassan: NO financial relationship with a commercial interest | Paola Spaggiari: NO financial relationship with a commercial interest | Luigi Terracciano: NO financial relationship with a commercial interest | Alessandro Repici: No Answer.