Serum ubiquitin levels in patients with nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis is increasingly recognized as the most common liver disease in patients with elevated liver enzymes. In the pathophysiology of nonalcoholic steatohepatitis, the first step is the lipid accumulation in the liver causing steatosis, the second step involves the endotoxins, cytokines and environmental toxins causing oxidative stress and lipid peroxidation, in time leading to steatohepatitis. Ubiquitin is a molecular chaperone that plays a major role in the degradation of intracellular proteins. Ubiquitin proteasome system is also considered as a cellular defense mechanism that removes damaged proteins generated by oxidative stress. In order to search for the role of ubiquitin in the pathogenesis of nonalcoholic steatohepatitis, serum levels of ubiquitin were studied in patients with nonalcoholic steatohepatitis for the first time in the literature, to our knowledge.

Eighteen patients with biopsy proven nonalcoholic steatohepatitis diagnosis (13 males and 5 females with a mean age of 41) and 16 healthy volunteers as a control group (11 males and 5 females, with a mean age of 38) were included in the study. Serum ubiquitin levels were studied by ELISA method.

The mean serum ubiquitin level (14.13 +/- 1.46 micrograms/mL) in patients with nonalcoholic steatohepatitis was significantly elevated compared to that of the control group (7.66 +/- 0.40 micrograms/mL) (p < 0.001). No correlation was found among serum ubiquitin levels and hepatic steatosis, inflammation and fibrosis.

Increased serum ubiquitin levels may show that the ubiquitin proteasome pathway actively participates in defending against oxidative stress in nonalcoholic steatohepatitis. Serum ubiquitin concentration may be a marker predicting the intracellular cytoprotective response against oxidative stress rather than the degree of liver damage in pathogenesis of nonalcoholic steatohepatitis. Ubiquitin proteasome system based therapies may have a place in the treatment of patients with nonalcoholic steatohepatitis in the future.