AMA-NEGATIVE PRIMARY BILIARY CHOLANGITIS IN LATIN AMERICA: A DISTINCT SUBSET WITH LOWER TREATMENT RESPONSE

Abstract

Primary biliary cholangitis (PBC) is an autoimmune cholestatic disease, typically diagnosed by the presence of anti-mitochondrial antibodies (AMA). Whether AMA-negative PBC represents a distinct clinical phenotype remains controversial. This study aimed to characterize the epidemiological profile of PBC according to AMA status in Latin America. This ongoing, retrospective, international multicenter cohort study, sponsored by ALEH, includes PBC patients from multiple Latin American countries. Patients were stratified by AMA status; those with autoimmune hepatitis-PBC overlap were excluded. Data from 1,204 patients were analyzed: Brazil (48.3%), Argentina (23.4%), Chile (10.8%), Mexico (7.4%), and others. Most were female (92.3%) with a mean age at diagnosis of 53±13 years; 22.2% had cirrhosis at baseline. Overlap syndrome was excluded. AMA were positive in 76.8%. AMA-positive and AMA-negative patients had similar rates of female sex (92.5% each, p=0.963), baseline cirrhosis (22.4% vs. 23.6%, p=0.706), and symptomatic presentation (77.5% vs. 79.4%, p=0.544). MASLD was more frequent among AMA-negative patients (7.5% vs. 3.8%, p=0.024), which also had higher rates of sp100 (9.1% vs 2.5%, p< 0.001) and gp210 (7.3 vs 3.3%, p< 0.001) positivity. Treatment with UDCA was performed in 95.2% of patients and, from those, 28.3% had second line treatment indicated due to incomplete response to UDCA. AMA-positive patients showed higher response to ursodeoxycholic acid (UDCA) at 12 months, including ALP normalization (29.7% vs. 21.2%, p=0.035) and deep response (17.5% vs. 8.6%, p=0.007). Similar findings were observed after 12 months of fibrate therapy (34.8% vs. 9.4%, p=0.005). No difference was found in transplant-free survival (p=0.213). AMA-negative PBC patients in Latin America present similar baseline features but have lower response rates to UDCA and fibrates, supporting the hypothesis of a biologically distinct disease subset.