Primary Biliary Cholangitis Unveiled by Positive Anti-Centromere Antibodies

Summary: Background Primary Biliary Cholangitis (PBC) is an autoimmune liver disease characterized by the immune-mediated destruction of small and medium intrahepatic bile ducts. The disease is distinguished by the presence of the anti-mitochondrial antibody (AMA) in 90-95% of patients. Antinuclear antibodies (ANAs) could be present in around 50% of cases. Additionally, up to 30% of PBC patients feature positive Anti-Centromere Antibodies (ACA), rising to 80% in PBC/Systemic Sclerosis (SSc) overlap syndromes. Case Presentation A 20-year-old primigravida at 28 weeks gestation was transferred from an outside hospital where she had been admitted for a twenty-day history of nausea, non-bloody emesis, dehydration, and pruritus without abdominal pain, fever, chills, or diarrhea. On arrival, the patient was asymptomatic except for continued pruritus. Laboratory findings demonstrated acute kidney injury, leukocytosis, and hypokalemia (K 2.6), along with markedly elevated total bilirubin (3.7 mg/dL), AST (1251 U/L), ALT (1890 U/L), and alkaline phosphatase (170 IU/L) with an unremarkable right upper quadrant ultrasound. Further work-up revealed low IgG levels (547 mg/dL,), positive ANA (1:160), and positive anti-centromere antibodies. Serological tests for viral hepatitis and other infections were negative. On evaluation, the patient denied symptoms associated with systemic sclerosis, including Raynaud’s phenomenon. The physical exam was also unrevealing. She had no laboratory abnormalities before this event. During hospitalization, an echocardiogram was unremarkable with no signs of pulmonary hypertension. After rheumatology evaluation, anti-mitochondrial M2 antibodies returned elevated with negative anti-smooth muscle antibodies. The patient was started on ursodiol with improvement of the symptoms and liver enzyme levels. She was discharged to follow up with outpatient hepatology. Discussion PBC is characterized by the immune-mediated destruction of intrahepatic bile ducts and often presents with a spectrum of symptoms ranging from nausea, vomiting, jaundice, and pruritus with a cholestatic liver enzyme pattern. In this case, the patient presented with a mixed hepatocellular injury with an R factor > 5.5 and an absence of jaundice broadening the differential diagnosis. This condition often coexists with other autoimmune disorders, with sicca syndrome and autoimmune thyroiditis being the most common. While PBC is frequently reported as the predominant liver disease in systemic sclerosis (SSc) patients, approximately 25% of SSc patients may test positive for anti-mitochondrial antibodies, a hallmark of PBC. Despite this known association, the overlap syndrome between systemic sclerosis and PBC does not always occur. In some cases when AMA and AMA-M2 are negative, ANA and ACA positivity suggests the possibility of early PBC. It's crucial to consider the possibility of PBC in patients with ACA positivity and liver injury, as prompt recognition can guide proper management and improve outcomes. In a subset of patients, PBC/SSc overlap syndrome occurs. Patients with this overlap phenotype may show a slower rate of liver disease progression compared to those with PBC. Conclusion The significance of positive anti-centromere antibodies (ACA) in the context of abnormal liver tests cannot be overstated, as it may correlate with the presence of primary biliary cholangitis (PBC). Our case highlights an atypical presentation of PBC where ACA positivity can help aid in diagnostics and assist in early treatment initiation. References 1.Caramaschi, P. et al. (2006a) ‘Coexistence of systemic sclerosis with other autoimmune diseases’, Rheumatology International, 27(4), pp. 407–410. doi:10.1007/s00296-006-0207-3. 2.Zhu, Y.-J. et al. (2023) ‘Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis’, World Journal of Gastroenterology, 29(34), pp. 5075–5081. doi:10.3748/wjg. v29.i34.5075. 3. Liberal, R. et al. (2013a) ‘Diagnostic and clinical significance of anti-centromere antibodies in primary biliary cirrhosis’, Clinics and Research in Hepatology and Gastroenterology, 37(6), pp. 572–585. doi: 10.1016/j.clinre.2013.04.005.