Predictors of Nonalcoholic Steatohepatitis in Japanese Patients: Thioredoxin and NASH

Abstract

To clarify the biochemical markers to discriminate between nonalcoholic steatohepatitis (NASH) and simple steatosis in Japanese patients and to clarify the clinicopathological features of NASH, we analyzed patients with NASH and simple fatty liver (FL). Seventy-five patients with biopsy-proven NASH and 53 patients with biopsy-proven FL were enrolled. Their clinical characteristics and histological findings were compared. Detection of GB virus (GBV) RNA and SEN virus (SENV) DNA was performed by polymerase chain reaction (PCR). Mutational analysis of the HFE gene was performed by PCR-restriction fragment length polymorphism. As a marker of oxidative stress, serum thioredoxin (TRX) levels were determined. Insulin resistance was evaluated by a homeostasis model assessment of insulin resistance (HOMAIR). Serum TRX levels were significantly elevated in patients with NASH, compared with patients with FL. GBV was detectable in the serum of only one patient with NASH. SEN virus was detected in 50% (15/30) of the patients tested, but the prevalence was not significantly different between the two groups (42% [8/19] in FL and 64% [7/11] in NASH). The HFE gene was not detected in any patient.We constructed a receiver operating characteristic (ROC) curve which confirmed that serum TRX and ferritin levels were predictors for distinguishing NASH from FL. HOMA-IR was higher in NASH patients than in FL patients. The pathogenesis of NASH may be associated with insulin resistance and iron-related oxidative stress. The serum TRX level is a parameter for discriminating NASH from simple steatosis.