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Treatment of primary biliary cholangitis (PBC) can improve the GLOBE score. We aimed to assess the association between changes in the GLOBE score (ΔGLOBE) and liver transplantation (LT)-free survival in patients with PBC who were treated with ursodeoxycholic acid (UDCA).Among UDCA-treated patients within the Global PBC cohort, the association between ΔGLOBE (ΔGLOBE0-1: during the first year of UDCA, ΔGLOBE1-2: during the second year) and the risk of LT or death was assessed through Cox regression analyses.Overall, 3,775 UDCA-treated patients were included; 3,424 (90.7%) were female, the median age was 54.0 (interquartile range [IQR] 45.9-62.4) years, and the median baseline GLOBE score was 0.25 (IQR -0.47 to 0.96). During a median follow-up of 7.2 (IQR 3.7-11.5) years, 730 patients reached the combined end point of LT or death. The median ΔGLOBE0-1 was -0.27 (IQR -0.56 to 0.02). Cox regression analyses, adjusted for pretreatment GLOBE score and ΔGLOBE0-12, showed that ΔGLOBE was associated with LT or death (adjusted hazard ratio 2.28, 95% confidence interval 1.81-2.87, P0.001). The interaction between baseline GLOBE score and ΔGLOBE0-1 was not statistically significant (P = 0.296). The ΔGLOBE1-2 was associated with LT or death (adjusted hazard ratio 2.19, 95% confidence interval 1.67-2.86, P0.001), independently from the baseline GLOBE score and the change in GLOBE score during the first year of UDCA.UDCA-induced changes in the GLOBE score were significantly associated with LT-free survival in patients with PBC. While the relative risk reduction of LT or death was stable, the absolute risk reduction was heavily dependent on the baseline prognosis of the patient.

Objectives: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival. Methods: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates. Results: During 8.1 years' median follow-up, 278 of 3,224 patients developed ascites, variceal bleeding, and/or encephalopathy (incidence rate of 9.7 cases/1,000 patient years). The overall cumulative incidence was 9.1% after 10 years of follow-up, but decreased over time to 5.8% after the year 2000. Earlier calendar year of diagnosis (P0.54 after 12 months of UDCA had a 10-year complication rate of 37.4%, as compared to 3.2% in biochemical responders with an APRI ≤0.54. The 10-year transplantation-free survival after a complication was 9% (time-dependent hazard ratio 21.5; 20.1-22.8). Prognosis after variceal bleeding has improved over time. Conclusions: In this large international cohort, up to 15% of UDCA-treated PBC patients developed major non-neoplastic, cirrhosis-associated hepatic complications within 15 years, but cumulative incidence has decreased over time. Biochemical non-response to UDCA and APRI were independent risk factors for these complications. Subsequent long-term outcome after complications is generally poor, but has improved over the past decades.

Hypercholesterolemia is a common finding in primary biliary cirrhosis (PBC), but the risk of cardiovascular events in PBC patients is not increased in respect to the general population. High serum adiponectin levels appear to play a protective role in the development of either metabolic syndrome or cardiovascular disease.To investigate factors potentially preventing atherosclerosis in PBC patients.Circulating levels of adiponectin, resistin, leptin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 137 consecutive PBC patients (125 women, 12 men; mean age 61.6 +/- 12.3 yr), 137 sex- and age-matched healthy controls, and 30 female patients with nonalcoholic steatohepatitis (NASH) and associated metabolic syndrome.The body mass index (BMI) was comparable in the three groups, whereas total cholesterol was significantly higher in both PBC and NASH cases than in controls (221.6 +/- 50.5 mg/dL in PBC vs 221.7 +/- 39.7 mg/dL in NASH vs 209.8 +/- 39.2 mg/dL in controls, P0.05). Serum concentrations of adiponectin, resistin, and leptin were significantly higher in PBC patients than in either NASH cases or controls (P0.05). Among the PBC patients, only adiponectin correlated positively with histological progression of the disease (P= 0.001) and negatively with BMI (P= 0.01). Logistic regression analysis revealed that adiponectin correlated independently with age, BMI, Mayo score, and gamma-glutamyl transpeptidase.The high adiponectin concentrations observed in PBC patients should be regarded as a possible protective factor against atherogenesis. The search for further protective factors should be encouraged.

Noninvasive assessment of esophageal varices (EV) may improve the management of patients with cirrhosis and decrease both the medical and financial burden related to screening. In this multicenter, international study, our aim was to prospectively validate the use of the platelet count/spleen diameter ratio for the noninvasive diagnosis of EV.A total of 218 cirrhotic patients underwent screening endoscopy for EV. Platelet count/spleen diameter ratio ((N/mm3)/mm) was assessed in all patients and its diagnostic accuracy was calculated. On the basis of previous results, a platelet count/spleen diameter ratio cutoff of 909 was applied to this population. The diagnostic accuracy of the platelet count/spleen diameter ratio was further evaluated for both severity and etiology of disease subgroups.Prevalence of EV was 54.1%. The platelet count/spleen diameter ratio had 86.0% (95% CI, 80.7-90.4%) diagnostic accuracy for EV, which was significantly greater as compared with either accuracy of platelet count alone (83.6%, 95% CI 78.0-88.3%, P= 0.038) or spleen diameter alone (80.2%, 95% CI 74.3-85.3%, P= 0.018). The 909 cutoff had 91.5% sensitivity (95% CI 85.0-95.9%), 67.0% specificity (95% CI 56.9-76.1%), 76.6% positive predictive value, 87.0% negative predictive value, 2.77 positive likelihood ratio, and 0.13 negative likelihood ratio for the diagnosis of EV. Accuracy of the platelet count/spleen diameter ratio was maintained for both severity and etiology of disease subgroups.The platelet count/spleen diameter ratio may be proposed as a safe and reproducible means to improve the management of cirrhotic patients who should undergo screening endoscopy for EV.

Autoimmune hepatitis/primary sclerosing cholangitis (AIH/PSC) overlap syndrome is a relatively uncommon variant of PSC.To evaluate the natural history of AIH/PSC overlap syndrome compared to a group of "classical" PSC.Forty-one consecutive PSC patients, with a regular follow-up of at least 2 years, were prospectively included in the study. Among these, 7 fulfilled the criteria for AIH/PSC overlap syndrome.The AIH/PSC overlap group significantly differed from the "classical" PSC group in the following parameters: mean age at presentation (21.4 +/- 5.0 vs 32.3 +/- 10 years, p0.01), AST 191.0 +/- 14.8 vs 48.9 +/- 34.5 U/L, p0.005), ALT (357.0 +/- 26.5 vs 83.7 +/- 60.7 U/L, p0.005) and serum IgG (25.6 +/- 4.7 vs 12.9 +/- 6.0 mg/dl, p0.0001). The mean follow-up was similar in the 2 groups (93.3 +/- 65.9 vs 98.1 +/- 65.9 months respectively). Treatment included immunosuppression + ursodeoxycholic acid (UDCA) in the AIH/PSC overlap patients, and UDCA in the "classical" PSC group. Deaths were recorded only in the classical PSC group. The median survival in the latter group was 207 months (95% C.I. 87.6-326.4). The major events during the follow-up included: OLTx (1/7 vs 6/34), and neoplasms (only in the group of "classical" PSC). The new Mayo score prognostic index only increased significantly during follow-up in the "classical" PSC group (r2 0.8117, p0.01)Patients with AIH/PSC overlap syndrome seem to benefit from immunosuppression + UDCA therapy, survival is apparently better than in "classical" PSC condition.