Bonder, Alan

ABSTRACT Background and Aims Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease with a high risk of malignancy and limited therapeutic options. Both the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend structured baseline evaluation, fibrosis staging and longitudinal surveillance. However, real‐world adherence to these practices in North America remains unclear. Methods We conducted a retrospective cohort study of 1300 patients with PSC enrolled in the Consortium for Autoimmune Liver Diseases (CALiD) registry between 2018 and 2024 across 19 centres in North America. Guideline adherence was assessed for diagnostic measures at baseline (colonoscopy to establish IBD status and noninvasive fibrosis staging) and longitudinal surveillance (colonoscopy in PSC‐IBD, abdominal imaging for hepatobiliary cancer surveillance and CA 19‐9 testing). Prescribing patterns for ursodeoxycholic acid (UDCA) were also characterised. Multivariable logistic regression was used to evaluate demographic, clinical and socioeconomic predictors of adherence. Results At diagnosis, 78.8% of eligible patients with available data underwent colonoscopy to establish IBD status, and 45% underwent noninvasive fibrosis staging. During follow‐up, only 30%–35% of patients with PSC‐IBD underwent colonoscopy annually, while abdominal imaging for hepatobiliary cancer surveillance declined from 74% at Year 1 to 51% by Year 4. CA 19‐9 testing was documented in 47% over 5‐year period. UDCA was prescribed in 51% at baseline, with median dose of 12.5 mg/kg/day. Socioeconomic factors, including lower education and household income, were associated with reduced adherence, while cirrhosis strongly predicted completion of surveillance imaging. Conclusions Adherence to guideline‐based care in PSC remains suboptimal in North America Suboptimal adherence was observed for strongly recommended practices with longstanding guideline support (colonoscopy to establish IBD status; annual CRC surveillance in PSC‐IBD) as well as practices where guideline consensus has evolved more recently or where societies differ (baseline fibrosis assessment; hepatobiliary cancer imaging). Efforts to standardise care and address socioeconomic barriers are urgently needed to improve outcomes.

Bridging locoregional therapy (LRT) is widely used in liver transplant (LT) candidates with hepatocellular carcinoma (HCC) to minimize waitlist dropout and evaluate tumor biology. While transarterial chemoembolization (TACE) has historically been the predominant approach, the role of transarterial radioembolization (TARE) is expanding. Comparative effectiveness data for these 2 modalities as bridging strategies remain limited. This study assessed the trends, factors influencing therapy selection, and outcomes of transarterial bridging LRT. We conducted a retrospective cohort study of adult LT candidates with HCC listed in the Organ Procurement and Transplantation Network (OPTN) between 2016 and 2024 who received TACE or TARE as their sole bridging LRT. Inverse probability weighting (IPW) was applied to balance baseline covariates. Multivariable Fine–Gray competing risk regression and stratified Cox proportional hazards and logistic regression models were used to assess waitlist dropout, complete pathological necrosis (CPN), recurrence, and overall survival. Among 8367 patients, 5472 (65%) received TACE, and 2895 (35%) received TARE. TARE use increased significantly from 22.5% to 51.7% over the study period. TARE was more likely to be used among patients with MASLD, older age, and high tumor burden, and less likely in those with lower socioeconomic status. TARE recipients had a significantly lower risk of waitlist dropout (sHR 0.83, p <0.001) and a higher likelihood of achieving CPN (aOR 2.24, p <0.001). The overall survival did not differ significantly between groups (aHR 0.94, p =0.19). The use of TARE as bridging therapy in HCC LT candidates has surged and is influenced by socioeconomic factors, comorbidities, and tumor burden. TARE effectiveness has been demonstrated by its advantages in waitlist retention and tumor necrosis. Further studies are warranted to evaluate its impact on post-LT recurrence and to validate the cost-effectiveness among transarterial therapies.

Background and Aims: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. Approach and Results: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7–21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7–59.9, p < 0.001) when these 2 conditions were met. Conclusions: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.