[Positive antinuclear antibodies suggest a high inflammatory burden phenotype: a multicenter retrospective analysis...

Objective: To investigate the effect of antinuclear antibodies on the clinicopathological characteristics, short-term treatment response, and long-term prognosis of primary biliary cholangitis. Methods: A retrospective analysis was performed on 690 cases with primary biliary cholangitis who were treated in eight medical centers, including Nanjing Second Hospital, from January 2017 to October 2023, and were divided into a negative group (96 cases) and a positive group (594 cases) according to antinuclear antibody status. Propensity score matching (1∶1) was used to balance age and gender factors. The laboratory indicators, liver histological characteristics, short-term biochemical responses, and the occurrence of decompensated event conditions were compared between the two groups. An independent sample t-test was used for comparison between groups of continuous variables that conformed to normal distribution. The Mann-Whitney U test was used for comparison between groups of continuous variables with non-normal distribution. The χ² test or Fisher's exact test was used for comparison of categorical variables between the two groups. The Mann-Whitney U test was used for rank data.The log-rank test was employed to compare the differences between groups in the Kaplan-Meier survival analysis.The Cox proportional hazards model was used to analyze the risk factors affecting prognosis. The cut-off value of the numerical variable was determined by the receiver operating characteristic curve. Results: There were 96 cases following matching in each group. The levels of aspartate aminotransferase (88.10 U/L vs. 71.55 U/L), γ-glutamyl transferase (278.61 U/L vs. 144.00 U/L), alkaline phosphatase (229.98 U/L vs. 159.68 U/L), and immunoglobulin G (19.90 U/L vs. 17.73 U/L) were significantly increased (P <0.05). The proportion of patients with positive anti-gp210 antibodies and/or anti-SP100 antibodies was significantly higher than that of the anti-nuclear antibody-negative group (21.43% vs. 5.26%, P=0.005). Liver histology showed that the detection rate of epithelioid granuloma was higher in the anti-nuclear antibody positive group (37.50% vs. 22.92%, P=0.028), while the degree of interface inflammation (none/mild/moderate/severe:2.08%/8.33%/63.54%/26.04% vs. 18.75%/23.96%/36.46%/20.83%, P<0.001) and Nakanuma-hepatitis activity score (HA0/HA1/HA2/HA3: 2.08%/4.17%/58.33%/35.42% vs. 23.96%/18.75%/35.42%/21.88%, P<0.001) were significantly higher in the anti-nuclear antibody-negative group. There was no statistically significant difference in the 1-year biochemical response rate and the incidence rate of decompensation between the two groups (P>0.05). Multivariate Cox regression analysis showed that platelet count ≤0.3× upper limit of normal value, albumin count ≤0.6×upper limit of normal value, and fibrosis stage S≥S3 were independent risk factors for decompensation of cirrhosis in patients with primary biliary cholangitis. Conclusions: Patients with antinuclear antibody-positive primary biliary cholangitis exhibit a phenotype of "high inflammatory burden," suggesting that antinuclear antibody status may serve as a potential serological marker of disease activity, and its value in long-term prognosis and treatment decision-making needs to be further verified by prospective studies.