Background and Aims: Liver fibrosis holds a relevant prognostic meaning in primary biliary cholangitis (PBC). Noninvasive fibrosis evaluation using vibration‐controlled transient elastography (VCTE) is routinely performed. However, there is limited evidence on its accuracy at diagnosis in PBC. We aimed to estimate the diagnostic accuracy of VCTE in assessing advanced fibrosis (AF) at disease presentation in PBC. Approach and Results: We collected data from 167 consecutive treatment‐naïve PBC patients who underwent liver biopsy (LB) at diagnosis at six Italian centers. VCTE examinations were completed within 12 weeks of LB. Biopsies were scored by two blinded expert pathologists, according to the Ludwig system. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROCs) for AF (Ludwig stage ≥III). Effects of biochemical and clinical parameters on liver stiffness measurement (LSM) were appraised. The derivation cohort consisted of 126 patients with valid LSM and LB; VCTE identified patients with AF with an AUROC of 0.89. LSM cutoffs ≤6.5 and >11.0 kPa enabled to exclude and confirm, respectively, AF (negative predictive value [NPV] = 0.94; positive predictive value [PPV] = 0.89; error rate = 5.6%). These values were externally validated in an independent cohort of 91 PBC patients (NPV = 0.93; PPV = 0.89; error rate = 8.6%). Multivariable analysis found that the only parameter affecting LSM was fibrosis stage. No association was found with BMI and liver biochemistry. Conclusions: In a multicenter study of treatment‐naïve PBC patients, we identified two cutoffs (LSM ≤6.5 and >11.0 kPa) able to discriminate at diagnosis the absence or presence, respectively, of AF in PBC patients, with external validation. In patients with LSM between these two cutoffs, VCTE is not reliable and liver biopsy should be evaluated for accurate disease staging. BMI and liver biochemistry did not affect LSMs.

Objective: Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)‐specific T cell therapy in a cohort of hematological patients with PML.Methods: Between 2014 and 2019, 9 patients with a diagnosis of “definite PML” according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV‐specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen‐derived peptides.Results: None of the patients experienced treatment‐related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV‐specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow‐up.Interpretation: Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769–779

Background: The rising prevalence of gastric, biliary, and pancreatic surgeries has led to an increasing population of patients with surgically altered anatomy (SAA). In this setting, conventional endoscopic retrograde cholangiopancreatography (ERCP) is often limited by anatomical barriers, resulting in high rates of technical failure and complications. While device-assisted enteroscopy (DAE) has expanded therapeutic possibilities, its efficacy remains modest in complex reconstructions. Methods: This review analyzed recent literature from PubMed, Embase, and Scopus up to April 2025, focusing on diagnostic and therapeutic roles of endoscopic ultrasound (EUS) in SAA. Particular attention was given to cases where standard endoscopic, percutaneous, or surgical techniques failed and to studies comparing EUS-guided approaches with alternative modalities. Results: EUS has transitioned from a primarily diagnostic modality to a versatile therapeutic platform in SAA. Techniques such as EUS-guided rendezvous, antegrade drainage, and hepaticogastrostomy have shown technical and clinical success rates exceeding 80–90%, often comparable or superior to interventional radiology, while reducing the need for external drains. Innovative procedures, including EUS-directed transgastric ERCP (EDGE) and EUS-directed enteroenteric bypass (EDEE), have transformed the management of Roux-en-Y gastric bypass and bilioenteric anastomoses, providing durable and reusable access for repeated interventions. Despite these advances, EUS-guided interventions remain technically demanding, requiring advanced endoscopic and radiologic skills, specialized devices, and are best performed in tertiary referral centers. Conclusions: EUS has redefined the treatment paradigm of biliopancreatic diseases in patients with SAA, increasingly emerging as the preferred minimally invasive approach when conventional techniques fail. Future developments will focus on dedicated devices, standardized guidelines, and structured training programs to optimize outcomes. Multidisciplinary collaboration and centralization in high-volume centers remain essential to ensure safety, efficacy, and reproducibility.

Introduction: Primary Biliary Cholangitis (PBC) is a chronic liver disease characterized by intrahepatic biliary destruction and progressive cholestasis potentially leading to end-stage liver disease and its associated complications. As for many chronic disorders, the risk of disease progression in PBC varies between patients. This has fostered the identification of disease tags defining the trajectory of the disease course. Areas covered: In this review, authors report the evidence-based parameters associated with outcomes in PBC, after an extensive literature search of the PubMed electronic database. Expert opinion: Several prognostic tools including clinical and biochemical disease parameters have been proposed. In the era of the omics science and digital innovation, biomarker discovery has sped up. Extensive data and sample collection of well-phenotyped cohorts of patients with longitudinal follow-up will guarantee an extraordinary opportunity to integrate molecular phenotyping into the clinic, thus promoting a personalized care of patients with PBC. Finally, we emphasize the need to leverage a therapeutic window of opportunity in PBC bringing a paradigm shift toward early intervention with combination therapies in individuals with a more severe phenotype to reach a deeper disease control and halt disease progression.