Plamatic levels of Coenzyme Q10 in primary biliary cirrrhosis

MARTINEFSKI M; DARUICH J; PUZZIO, C; DI CARLO M.B; GONZALEZ BALLERGA, E; TRIPODI V.; SORDA J

Congreso; The 63rd Annual Meeting of the American Association for the Study of Liver Diseases; 2012

Introduction: Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. Ursodeoxicholic acid (UDCA) is the widely approved therapy. Due of the cholestasis hydrophobic bile acids (BA) are accumulated in liver and plasma. On the other hand, cholestasis is associated with profound metabolic changes including alterations in the mitochondrial function. Coenzyme Q10 (CoQ10) is a lipid-soluble molecule mainly located into the inner membrane of the mitochondria where plays a key role in mitochondrial energy production. CoQ10 is recognized as a powerful natural antioxidant and anti-inflammatory agent. Objective: to investigate the plasmatic CoQ10 levels and its relation to hydrophobic BA in PBC before and after treatment. Materials and Methods: All patients included had a liver biopsy, AMA, AMA2 and laboratory tests compatible with the diagnosis of PBC. It was included 7 PBC (Stages I-II: 7) patients before treatment, 19 PBC (Stages I-II: 7, 36.8% and stage III-IV: 12, 63.2%) patients with long term UDCA treatment (>2 years, 15 mg/kg/day) and 22 age- and sex-matched healthy controls. It was used capillary electrophoresis to determine serum bile acid profiles and micro-HPLC for CoQ10 determinations. Results: It was found that non-treated PBC patients have a significant decrease in plasma CoQ10 levels as compared to control subjects (0.20±0.03 vs 0.47±0.04 µM, mean±SEM, p<0.01). Furthermore, this CoQ10 reduction was associated to an increase of plasma hydrophobic BA, mainly lithocholic acid (LCA) (5.20±1.44 vs 0.28±0.05µM, mean±SEM, p<0.003). On the other hand, patients with long-term UDCA treatment showed a non-significant decrease plasmatic LCA levels compared to untreated patients (3.16±0.59 µM, mean±SEM) which correlated with a trend of increase in CoQ10 (0.24±0.03 µM, mean±SEM, r=-0.5707, p<0.03), although neither CoQ10 nor LCA reached normal values. Conclusion: The recognition of CoQ10 deficiency in PBC could be an important issue. The combined use of UDCA and CoQ10 may act synergistically against the production of free radicals slowing the progression of the disease. Further studies are necessary to evaluate the relationship between CoQ10 and histologic findings, LCA levels, as well the potential beneficial effect in patients with PBC.