原発性胆汁性胆管炎

BACKGROUND & AIMS: We compared multibipolar radiofrequency ablation (mbpRFA) with open liver resection (OLR) or laparoscopic liver resection (LLR) in patients with HCCs within Milan. METHODS: This multicenter cohort study included patients treated by mbpRFA, OLR or LLR for HCC within the Milan Criteria, developed on advanced fibrosis in nine French centres between 2008 and 2018. Adjustments on HCC size/number, gender, age, ASA, HCV, HBV, metabolic syndrome, chronic alcohol intake, MELD score, serum AFP level, APRI score, cirrhosis, significant portal hypertension and HCC localization were performed using multivariable regressions with centre-robust variance and propensity score-based matching (3:1 nearest-neighbour with calliper < 0.1; effective ratios 2.18:1 and 2.43:1). RESULTS: 1040 patients were included (median age: 64 years; male 82.9%), with 606, 266 and 168 treated by mbpRFA, LLR and OLR. Most HCCs were solitary (84.8%) and on cirrhosis (89.2%). In months, the follow-up was 50.2 (95% CI: 45.3, 54.3), 43.3 (95% CI: 40.0, 48.6) and 47.4 (95% CI: 40.8, 58.7) for mbpRFA, LLR and OLR patients. After matching, OLR patients had similar overall survival (OS) (HR = 1.05 [CI 95% = 0.65, 1.69], p = 0.853), transplant-free survival (TFS) (HR = 0.91 [CI 95% = 0.56, 1.47]; p = 0.690) or recurrence-free survival (RFS) (HR = 0.99 [CI 95% = 0.69, 1.43]; p = 0.968) compared to mbpRFA patients but with more severe adverse events (RR = 2.58 [CI 95% = 1.16, 5.71]; p = 0.02) and mortality (RR = 4.51 [CI 95% = 1.16, 17.59]; p = 0.03). After matching, LLR patients had better OS (HR = 0.57 [CI 95% = 0.38, 0.88], p = 0.01) but similar TFS (HR = 0.77 [CI 95% = 0.55, 1.1]; p = 0.152) and more severe adverse events (RR = 2.61 [CI 95% = 1.15, 5.96]; p = 0.022) compared to mbpRFA patients. LLR patients had a better RFS (HR = 0.7 [CI 95% = 0.53, 0.91]; p = 0.009) than mbpRFA patients. When distant-only recurrences were considered in the mbpRFA patients, there was no significant difference in RFS (p = 0.087). The LLR survival benefit was consistent across pre-specified subgroups, with no interaction surviving correction for multiple testing. CONCLUSIONS: Minimally invasive modalities (LLR or mbpRFA) should be prioritized when treating early HCC. LLR maximizes oncological outcomes, but mbpRFA maintains optimal TFS with less morbidity.

Primary liver and biliary tract cancers remain major causes of global cancer mortality, with liver and intrahepatic bile duct cancers accounting for 866,136 new cases and 758,725 deaths worldwide in 2022. Curative surgery, transplantation, ablation, embolotherapy, and systemic therapy have improved outcomes, but many patients remain limited by cirrhosis, liver reserve, vascular invasion, biliary obstruction, anatomic constraints, or advanced presentation; population-level survival remains poor for both liver and bile duct cancers. Modern radiation therapy has emerged as an important local and regional modality for hepatocellular carcinoma, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.

In a recent publication, Lapitz et al. reported differences in serum levels that predict the development of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis prior to clinical manifestation. We examined whether these biomarkers also predict the risk of gallbladder cancer (GBC) in European prospective plasma samples from 24 GBC cases and 90 control individuals. After logarithmic transformation and quantile normalisation of individual protein levels measured with a timsTOF PRO mass spectrometer, we fitted univariate logistic regression models and applied backward model selection to identify the optimal model for GBC risk prediction. CRP and MASP2, previously reported markers of CCA, were found to be predictive for GBC risk as well (p value < 0.05), and complemented by age at blood sampling, provided an area under the receiver operating characteristic curve of 0.80 (95% confidence interval 0.69-0.92) when combined in a prediction model for GBC risk. We further examined the mRNA expression of CRP and MASP2 in serum samples from 82 GBC cases and 79 control subjects from Chile. CRP mRNA levels were elevated in Chilean GBC cases, but MASP2 showed an opposite trend. While there are considerable differences in the design of the discovery study and ours, the finding that circulating levels of CRP and MASP2 are associated with the risk of both CCA and GBC in Europeans highlights the need for further research into potential shared mechanisms and strategies for the prevention of these two aggressive biliary tumours.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) frequently impairs health-related quality of life (HRQOL); however, longitudinal changes in symptoms and their relationship with prognosis remain unclear. We aimed to elucidate the current status of symptoms and HRQOL in Japanese patients with PBC, evaluate 10-year changes in PBC-40 scores, and examine associations with long-term outcomes. METHODS: This multicenter observational study comprised three analyses: (i) a 2025 cross-sectional study assessing associations between clinical parameters, PBC-40 (symptom indicators), and EQ-5D-5 L (HRQOL indicators); (ii) a longitudinal PBC-40 study comparing scores from 2015 to 2025; and (iii) a longitudinal outcome study evaluating 2015 PBC-40 scores and clinical parameters in relation to survival through 2025. RESULTS: In 2025%, 20%-50% of all patients (n = 239) had moderate/severe PBC-40 scores in each domain. EQ-5D-5L scores were significantly lower in women < 59 years versus general population, with multivariable analysis identifying itch, fatigue, and social domains as independent contributors to impaired HRQOL. Across a 10-year follow-up, overall significant deterioration was observed in symptoms (p = 0.0015), itch (p = 0.0039), and cognitive (p = 0.0011) domains, while interindividual variability was greatest in itch and emotional and smallest in symptoms. In longitudinal outcome study (n = 410), no PBC-40 domain predicted death or liver transplantation. CONCLUSIONS: HRQOL in patients with PBC was significantly impaired in younger female. Over 10 years, overall and interindividual changes in domain scores greatly varied, suggesting that symptom burdens are driven by heterogeneous underlying mechanisms. HRQOL impairment represents distinct dimensions of disease impact in PBC, independently of long-term outcomes.

BACKGROUND: Vitamin D deficiency has been implicated in cancer risk across several organ systems, but its role in hepatobiliary malignancy (HBM) remains unclear. We evaluated whether vitamin D supplementation (VDS) was associated with a lower risk of HBM specifically in patients with primary sclerosing cholangitis (PSC). METHODS: Patients enrolled in the PSC registry at our quaternary care and liver transplant (LT) center from 2010 to 2020 were analyzed. The primary exposure was VDS, modeled as a time-dependent variable. The primary outcome was HBM. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics, and Cox proportional hazards models were employed to estimate marginal hazard ratios (HRs). Cumulative incidence functionsfor HBM were estimated using a competing risks analysis treating death, and LT was as competing events. RESULTS: A total of 160 patients (mean age 42 years; 66% male) were included, of whom 76 (47.5%) reported baseline VDS. Over a median follow-up of 7 years, 15 patients developed HBM, corresponding to an incidence rate of 12.3 per 1000 person-years. VDS was associated with a significantly lower risk of HBM in both conventional (HR 0.16, 95% CI 0.05-0.57) and IPTW (HR 0.15, 95% CI 0.03-0.41) analyses. This association was consistent across baseline vitamin D strata, including <30 ng/mL (HR 0.12, 95% CI 0.02-0.79) and ≥30 ng/mL (HR 0.18, 95% CI 0.05-0.65). Accounting for competing risks, the 5-year cumulative incidence of HBM was 1.1% among patients receiving VDS versus 11.5% without VDS (p<0.01). DISCUSSION: VDS was associated with a significantly lower risk of HBM in this longitudinally followed cohort of patients with PSC. These findings support the consideration of VDS in all patients with PSC and underscore the need for mechanistic and interventional studies to further evaluate this association.