Lindor, K D

SummaryBackgroundAfter 1 year of ursodeoxycholic acid (UDCA), patients with primary biliary cholangitis (PBC) may have a normal GLOBE score despite high alkaline phosphatase (ALP) levels.AimTo assess the association between ALP and liver transplantation (LT)‐free survival according to the GLOBE scoreMethodsAmong patients with a normal or elevated GLOBE score in the Global PBC cohort, the association between ALP after 1 year of UDCA and the risk of LT/death was assessed. The LT‐free survival was compared with that of a matched general population.ResultsAfter 1 year of UDCA, ALP was associated with the risk of LT/death (aHR 1.31, 95% CI 1.003–1.72, p = 0.048) among 2729 patients with a normal GLOBE score. The 10‐year LT‐free survival among these patients with an ALP >2.0 × ULN was 94.0% (95% CI 90.1–97.9) for those <50 years, and 82.6% (95% CI 76.5–88.7) for those ≥50 years, which was significantly lower (p = 0.040) and similar (p = 0.736) to that of the matched population, respectively. The 10‐year LT‐free survival in patients ≥50 years with normal GLOBE score and normal ALP (90.8%, 95% CI 87.7–93.9) was significantly higher (p = 0.022) than the matched population. Among 1045 patients with an elevated GLOBE score, ALP was associated with LT/death only in those <50 years (aHR 1.38, 95% CI 1.06–1.81, p = 0.016).ConclusionThe LT‐free survival of patients with PBC with a normal GLOBE score is optimal in case of normal ALP levels, also in relation to the general population. Despite their generally favourable prognosis, an elevated ALP level may still indicate a need for add‐on therapy.

AbstractBackground & AimsMachine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub‐phenotyping and risk stratification in primary biliary cholangitis (PBC).MethodsML was applied to an international dataset of PBC patients. The dataset was split into a derivation cohort (training set) and a validation cohort (validation set), and key clinical features were analysed. The outcome was a composite of liver‐related death or liver transplantation. ML and standard survival analysis were performed.ResultsThe training set was composed of 11,819 subjects, while the validation set was composed of 1,069 subjects. ML identified four clusters of patients characterized by different phenotypes and long‐term prognosis. Cluster 1 (n = 3566) included patients with excellent prognosis, whereas Cluster 2 (n = 3966) consisted of individuals at worse prognosis differing from Cluster 1 only for albumin levels around the limit of normal. Cluster 3 (n = 2379) included young patients with florid cholestasis and Cluster 4 (n = 1908) comprised advanced cases. Further sub‐analyses on the dynamics of albumin within the normal range revealed that ursodeoxycholic acid‐induced increase of albumin >1.2 x lower limit of normal (LLN) is associated with improved transplant‐free survival.ConclusionsUnsupervised ML identified four novel groups of PBC patients with different phenotypes and prognosis and highlighted subtle variations of albumin within the normal range. Therapy‐induced increase of albumin >1.2 x LLN should be considered a treatment goal.

SummaryBackground and AimsPSC is an autoimmune biliary inflammatory disorder that is often associated with inflammatory bowel disease (IBD), with 50%‐75% of patients with PSC having coexisting IBD, most commonly ulcerative colitis. Currently, no medical therapies have been shown to improve the disease course or slow its progression. However, ongoing research has resulted in a growing interest in the use of antibiotics for treatment of PSC, of which vancomycin is the most studied. In this review, we summarise the current evidence on the use of vancomycin in PSC and comment on future research areas of interest.MethodsA comprehensive PUBMED and EMBASE literature search for articles on vancomycin, PSC, therapeutic options and microbiome was performed.ResultsTwo randomised clinical trials, three case series and two case reports were included in the study. These include uncontrolled data from at least 98 patients that include promising improvements in biochemistry and imaging. Optimal dosing regimens are unclear.ConclusionVancomycin is one of the most studied antibiotics used in the treatment of PSC with promising results. There is not currently sufficient evidence to support treatment recommendations. Further research is needed to establish if vancomycin is a PSC treatment.