Background and Purpose—: Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods—: Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results—: Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA ₂ DS ₂ -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA ₂ DS ₂ -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61). Conclusions—: In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA ₂ DS ₂ -VASc score were associated with increased risk of cerebrovascular events.

Primary biliary cirrhosis (PBC) is a chronic cholestatic disease characterized by the presence of antimitochondrial antibodies (AMA). PBC-specific antinuclear antibodies (ANA) have been characterized and associated with disease progression and outcome. We evaluated the clinical significance of the presence and serial changes in titers of AMA, PBC-specific ANA (anti-gp210, anti-sp100) and anti-chromatin antibodies. Over a median (IQR) period of 35 (36) months, 512 specimens were collected from 110 patients. Autoantibodies were detected by commercial ELISAs (INOVA Diagnostics). Biochemical, clinical, and histological status were included at initial presentation and during follow-up visits. The Mayo risk score was calculated as a prognostic index at each time point. Liver biopsy findings were classified according to Ludwig’s classification and biochemical response to ursodeoxycholic acid was evaluated according to Pares. At baseline, AMA IgG and IgA, anti-gp210 IgG, anti-sp100 IgG and anti-chromatin IgG were detected in 92/110 (83.6%), 57/110 (51.8%), 5/110 (4.5%), 14/110 (12.7%), and 0/110 (0%) patients, respectively. Positivity for all autoantibodies apart from anti-chromatin, at baseline visit (n = 110 patients), in all tested sera (n = 512) as well as increased autoantibodies titers during follow-up were associated with biochemically and/or histologically advanced disease. A decrease of anti-sp100 titers but not of anti-gp210 titers during follow-up was associated with improvement of Mayo risk score (p = 0.025) and response to ursodeoxycholic acid (p = 0.016). These results suggest that detection of AMA and PBC-specific ANA was correlated with disease severity. Serial changes of anti-sp100 titers and not of anti-gp210 titers might prove useful for monitoring the disease course and treatment outcome.

Background: We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH/overlap syndromes and in cases with coexistence of AIH and other liver diseases. Methods: We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH, AIH/overlap syndromes and AIH with concurrent other liver disease namely, patients with chronic hepatitis B (n = 109), chronic hepatitis C (n = 95), chronic hepatitis D (n = 4), alchoholic liver disease (n = 28), non-alcoholic fatty liver disease (n = 55), autoimmune cholestatic liver diseases (n = 77), liver disorders of undefined origin (n = 32) and with miscellaneous hepatic disorders (n = 23). 24 patients with AIH associated with any kind of liver disorder including 10 patients with AIH/overlap syndromes and 14 AIH with concurrent other liver disease were also investigated. 43 patients with AIH consisted the control group. Results: The specificity of the score was 98.1% while the sensitivity in unmasking AIH in patients with either AIH/overlap syndromes or AIH with concurrent other liver diseases was only 50% and 78.6%. In the binary logistic regression model, the presence of other autoimmune diseases (p < 0.001), the total histological score (p < 0.001) and positivity for autoantibodies (p < 0.05) were identified as independent predictors for the presnce of AIH/ovea syndromes o AI with concurren other liver diseass. Conclusion: The IAHG scoring system has very good specificity for excluding AIH in patients with chronic liver diseases but not that sensitivity in order to unmask AIH/overlap syndromes or AIH with concurrent other liver diseases. The presence of other autoimmune diseases or autoantibody markers in the absence of hepatitis viral markers should alarm physicians for the possible presence of AIH either as "pure" AIH or in association with other liver disorders (AIH/overlap syndromes or AIH with concurrent other liver diseases). Under these conditions, liver histology seems essential and it must always be included in the work up of hepatic patients.