Using two-step cluster analysis to classify inpatients with primary biliary cholangitis based on autoantibodies: A real-world retrospective study of 537 patients in China

Abstract

BackgroundA variety of autoantibodies have been detected in primary biliary cholangitis (PBC), while the presence of autoantibody clusters and their clinical significance have not been fully understood. We aimed at defining autoantibody clusters and to better understand the clinical features and prognosis of PBC patients based on autoantibody clusters under real-world conditions.MethodsWe retrospectively analyzed 788 inpatients with PBC evaluated between October 2008 and July 2019, and included 537 patients. Nineteen autoantibodies which were measured routinely were investigated for cluster analysis. Two-step clustering, Kaplan-Meier survival, and Cox regression analyses were used.ResultsFive clusters were defined. A cluster of antinuclear antibodies (ANA) and anti-gp210 positive patients were identified with a high rate of cirrhosis at baseline and low survival rate; a cluster of ANA, anti-centromere antibodies (ACA) and/or anti-CENP-B female dominant patients with older disease onset, low level of platelet count at baseline, high rate of hepatic decompensation, and low survival rate was also characterized; and another cluster of anti-mitochondrial antibodies (AMA) and/or AMA-M2, anti-Ro52 and a high rate of anti-gp210 positive patients were identified with a high proportion of male patients and low survival rate. A subgroup of patients with anti-SSA and/or anti-SSB coexists with SjS was also identified; patients with only AMA and/or AMA-M2-positive with a benign clinical outcome and relatively high complication of non-alcoholic fatty liver disease (NAFLD) were also identified. Only anti-gp210 was considered as a significant predictor for poor outcomes especially in patients with cirrhosis.ConclusionClustering methods allow the identification of distinct autoantibody profiles of PBC that form clinical subsets and can be useful for personalized approaches to diagnosis, clinical management, and the prediction of clinical outcomes. Anti-gp210 was the strongest predictive factor for poor outcomes especially in PBC patients with cirrhosis under real-world conditions.

Prevalence and prognostic significance of main metabolic risk factors in primary biliary cholangitis: a retrospective cohort study of 789 patients

“…The findings are in line with the conclusion of a recent study we conducted, which examined the clinical characteristics and prognosis of PBC patients using autoantibody clusters in real-world settings. Our study found that patients who tested positive only for AMA and/or AMAM2 had a higher incidence of NAFLD complications but a better overall disease prognosis than other PBC patients (42).…”

Risk Stratification in Primary Biliary Cholangitis

“…The prognostic role of anti-gp210 antibodies has been recently confirmed in a large cohort study [66]. Therefore, the inclusion of anti-gp210 antibodies into the UK-PBC and GLOBE scoring systems could potentially enhance their risk stratification capabilities [67].…”