Primary biliary cirrhosis is associated with oxidative stress and endothelial dysfunction but not increased cardiovascular risk

Abstract

Aim: Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which is associated with hypercholesterolaemia. Further, cholestatic diseases are associated with deficiencies of anti‐oxidant vitamins. Despite these associations PBC is not associated with an increase in cardiovascular mortality. The aim of this study is to assess if primary biliary cirrhosis is associated with oxidative stress, endothelial dysfunction and alteration of vascular compliance which is a surrogate marker for cardiovascular risk. Methods: Fifty‐one PBC patients and 34 control subjects were studied. Lipid soluble vitamins A, and E in addition to ascorbate and carotenoids were measured to assess anti‐oxidant status. C‐reactive protein, hydroperoxides and adhesion molecules sICAM‐l/sVCAM‐l were assessed as serological measures of endothelial function. Finally, measures of vascular compliance were assessed by applanation tonometer. Results: CRP, sICAM and sVCAM were all significantly higher in PBC patients (469.14 vs 207.13, P < 0.001; 768.12 vs 308.03,P < 0.001; 708.40 vs 461.31, P < 0.001) whilst anti‐oxidant vitamin levels were lower in PBC patients, with ascorbate, vitamin E and vitamin A all significantly lower in PBC patients (39.91 vs 72.68, P < 0.001; 2.63 vs 3.14, P = 0.02; 1.08 vs 1.81, P < 0.001). Despite these findings PBC patients have a lower pulse wave velocity than control subjects (8.22 m/s vs 8.78 m/s, P = 0.022). Conclusion: PBC patients appear to have reduced vascular risk as assessed by pulse wave velocity but concurrently have evidence of endothelial dysfunction, inflammation and anti‐oxidant deficiency.

Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies: Toward Mitochondria-Targeted Clinical Strategies

“…Patients with primary biliary cirrhosis (PBC) display decreased levels of antioxidant vitamins (A, C and E), excess HOCl release associated with eosinophil peroxidase, and decreased GST expression [255–257]. The autoimmune condition in PBC was found to show IgG production against lipid peroxides and serum and saliva AMA against E2 subunits of 2-oxoacid dehydrogenase enzymes (pyruvate dehydrogenase complex, 2-oxo-acid dehydrogenase, and 2-oxo-glutarate dehydrogenase) pointing to autoimmune onset of MDF [258].…”

Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort

“…Essentially, 75% of the patients in our series had a total cholesterol value greater than the normal values (> 200 mg/dL). Even if the risk of mortality from cardiovascular disease is not increased in patients with PBC, despite the presence of hypercholesterolemia (40), we reported two deaths for cardiovascular events during follow-up.…”

Adult Stem Cell Therapy in Chronic Liver Diseases

“…Excessive reactive oxygen species (ROS) induces liver diseases such as liver fibrosis, cirrhosis, viral hepatitis, hepatocellular carcinoma (HCC) and others through oxidative disease [43]. Carbon tetrachloride (CCl4) and thioacetamide (TAA) are toxins used to generate liver injury in animal models [44].…”