Autoimmune Liver Diseases and Antiphospholipid Antibodies Positivity: a Meta-analysis of Literature Studies

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Pasquale Ambrosino1, Roberta Lupoli1, Gaia Spadarella1, Paolo Tarantino1,
Alessandro Di Minno1, Luciano Tarantino2*, Matteo Nicola Dario Di Minno1,3*

1) Department of Clinical Medicine and Surgery, Federico II University, Naples
2) Department of Surgery, Interventional Hepatology Unit, Andrea Tortora Hospital, Pagani
3) Unit of Cell and Molecular Biology in Cardiovascular Diseases, Centro Cardiologico Monzino, IRCCS, Milan, Italy
*The two authors share co-seniorship of this study



Background & Aims:
Several studies reported an association between autoimmune liver diseases (AiLD) and antiphospholipid antibodies (aPL) positivity. We performed a meta-analysis of studies evaluating the association of primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC) with aPL positivity and with aPL-related thrombotic events.

Methods: Studies evaluating the association of AiLD with aPL (anticardiolipin [aCL], anti-β2 glycoprotein-I [anti-β2GPI], lupus anticoagulant [LA] antibodies) and with aPL-related thrombotic complications were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases.

Results: A total of 10 studies (750 patients with AiLD and 1,244 healthy controls) were included in the analysis on the prevalence of aPL and showed that AiLD are significantly associated with the presence of aCL and anti-β2GPI. The association with aCL positivity was consistently confirmed in PBC (OR: 13.93, 95%CI: 4.69-41.38), AIH (OR: 23.50, 95%CI: 4.28-129.13), and PSC (OR: 18.21, 95%CI: 7.05-47.08). Similarly, anti-β2GPI were found more frequently in PBC (OR: 25.10, 95%CI: 4.77-132.11), AIH (OR: 48.57, 95%CI: 11.07-213.09), and PSC (OR: 36.30, 95%CI: 6.55-201.31). These findings are confirmed when separately analyzing IgM, IgG, and IgA directed against phospholipids. Two of the 10 included articles and 1 further study (67 cases and 75 controls) showed a trend - not achieving statistical significance - towards a higher prevalence of thrombotic complications in AIH patients with aPL as compared to those with only AIH (OR: 1.67, 95%CI: 0.46-6.05).

Conclusion: PBC, AIH, and PSC are significantly associated with aPL positivity. The association with aPL-related thrombotic complications should be further studied.

Key words: primary biliary cirrhosis - autoimmune hepatitis - primary sclerosing cholangitis - antiphospholipid antibodies - antiphospholipid syndrome.