Primary biliary cirrhosis is characterized in 95% of patients by autoantibody responses directed against the mitochondrial antigen pyruvate dehydrogenase complex.
Dr Kieren Hollingsworth and colleagues examined mitochondrial function and pH regulation in peripheral muscle during exercise.
They compared patients with PBC to patients with chronic fatigue syndrome, primary sclerosing cholangitis (PSC) and to normal controls.
The team found that all subjects except those with PBC exhibited a close correlation between kinetics of adenosine diphosphate and phosphocreatine recovery after low-impact exercise.
This relationship was lost in PBC patients, indicating mitochondrial dysfunction.
|At higher levels of exercise PBC patients showed excess muscle acidosis.|
|Clinical Gastroenterology and Hepatology|
Furthermore, the ratio between phosphocreatine and adenosine diphosphate recovery half-times was significantly elevated in PBC patients. This was associated with anti- pyruvate dehydrogenase complex levels.
The researchers also found that at higher levels of exercise PBC patients showed excess muscle acidosis, indicating a link to mitochondrial dysfunction.
The PBC patients also showed significant prolongation of muscle pH recovery time after exercise. This correlated with clinical fatigue.
Dr Hollingsworth’s team concluded, “PBC patients exhibit a variable degree of muscle mitochondrial dysfunction that manifests as excess acidosis after exercise”.
“The extent to which patients can recover rapidly from acidosis appears to determine whether they are clinically fatigued.”