Characteristics of AMA-M2(+) and SP100/GP210(+) primary biliary cholangitis (PBC) at diagnosis and their impact on prognosis

Background and Aims:

Primary biliary cholangitis (PBC) represents a rare liver disease and diagnosis can be challenging. However, auto-antibody testing for anti-mitochondrial antibodies, type M2 (AMA-M2) and anti-nuclear antibodies, such as of spotted pattern (SP100) and the anti-glycoprotein-210 (GP210) have been integrated in PBC diagnosis and may also have prognostic implications.

Methods:

Patients undergoing AMA-M2, SP100 or GP210 testing at the Medical University of Vienna between 02/2005 – 11/2018 were assessed for positive results. A diagnosis of PBC was established in case of any PBC-specific autoantibodies in combination with elevated alkaline phosphatase (AP) levels in absence of mechanical cholestasis. Demographics, presence/severity of laboratory abnormalities, and course of liver disease were recorded for AMA-M2(+) and AMA-M2(-) PBC patients. Survival was calculated by Kaplan-Meier curves and compared by log-rank tests.

Results:

Among 6718 patients tested, 588 (8.8%), 252 (3.8%) and 101 (1.5%) were positive for AMA-M2, SP100 and GP210, respectively. Based on elevated AP, 308 patients with AMA-M2(+) and 74 patients with AMA-M2(-) PBC were identified. In AMA-M2(+) PBC patients, 153/308 (49.7%) and 43/308 (14.0%) had Ap ≥1.67xULN and bilirubin levels > 1.5 mg/dL, while in AMA-M2(-) PBC, 33/74 (44.6%) and 12 (16.2%) had Ap ≥1.67xULN and bilirubin> 1.5 mg/dL at diagnosis. 22 PBC patients also presented with serological features of AIH overlap (anti-LKM1/SLA/SLA/LC1 with AST/ALT elevations). Bilirubin levels > 1.5 mg/dL (n = 55, 14.4%) and advanced fibrosis (n = 65, 17.0%; based on FIB4> 3.25) at presentation was associated with significantly worse overall survival (both log-rank p < 0.0001) after diagnosis. In turn, achieving AP< 1.67 during follow-up was associated with significantly improved survival (log-rank p < 0.0001) as compared to PBC patients remaining at Ap ≥1.67xULN.

Fig. 1

Conclusions:

Among 308 and 74 patients with AMA-M2(+) or AMA-M2(-) PBC 55 (14.4%) had bilirubin levels > 1.5 mg/dL and 65 (17.0%) advanced fibrosis: These features predicted worse survival, while achieving AP levels < 1.67xULN indicated an improved prognosis. The impact of PBC-specific ANA will be further analysed.