Insulin resistance/beta-cell function and serum ferritin level in non-diabetic patients with hepatitis C virus infection.

BACKGROUND/AIMS: Since impaired glucose tolerance and iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases, in this study we investigated insulin resistance, pancreatic beta-cell function, i.e., insulin secretion, and serum ferritin levels in patients with HCV infection, especially non-diabetic patients. METHODS: Homeostasis model assessments for insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta) were performed in 92 HCV-infected patients. RESULTS: The levels of plasma immunoreactive insulin (IRI), HOMA-IR, and HOMA-beta were significantly correlated with fasting plasma glucose (FPG) levels. Among the 86 non-diabetics (with an FPG of <126 mg/dl), IRI, HOMA-IR, and HOMA-beta were significantly higher in patients with liver cirrhosis than in patients with persistently normal alanine aminotransferase levels. The IRI and HOMA-IR values, but not the HOMA-beta values, were correlated with both serum transaminase and ferritin levels in the 65 non-diabetic chronic hepatitis patients. CONCLUSION: Insulin resistance was connected with impaired glucose tolerance and the severity of liver diseases in non-diabetic patients with HCV infection. Iron overload may be responsible for insulin resistance, or vice versa. Pancreatic beta-cell function was unrelated to the patients' serum ferritin levels.

Serum thioredoxin levels as a predictor of steatohepatitis in patients with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX in patients with nonalcoholic steatohepatitis (NASH) or simple steatosis. METHODS: Serum TRX levels were determined using an enzyme-linked immunosorbent assay kit in 25 patients with NASH, 15 patients with simple steatosis, and 17 healthy volunteers. RESULTS: Serum TRX levels (medians and (ranges), ng/ml) were significantly elevated in patients with NASH (60.3 (17.6-104.7)), compared to those in patients with simple steatosis (24.6 (16.6-69.7), P=0.0009) and in healthy controls (23.5 (1.3-50.7), P<0.0001). Serum ferritin levels in patients with NASH were also significantly higher than the levels in patients with simple steatosis. The receiver operating characteristic curve confirmed that serum TRX and ferritin levels were predictors for distinguishing NASH from simple steatosis. Higher grades of histological iron staining were observed in NASH than in simple steatosis. Serum TRX tended to increase in accordance with hepatic iron accumulation and the histological severity in patients with NASH. CONCLUSIONS: The pathogenesis of NASH may be associated with iron-related oxidative stress. The serum TRX level is a parameter for discriminating NASH from simple steatosis as well as a predictor of the severity of NASH.

Effects of glycyrrhizin on glucocorticoid signaling pathway in hepatocytes.

The cytoprotective effects of glycyrrhizin (GL) are similar to glucocorticoids. We investigated the effects of GL on the glucocorticoid receptor (GR) and on the enzyme activity of tyrosine aminotransferase (TAT), an hepatocyte-specific marker of glucocorticoid action, in rat hepatocytes. Pretreatment with GL significantly decreased the affinity of GRs for dexamethasone (DEX) and increased the period of time required for TAT activity to reach a peak after the addition of DEX. GL did not affect the amount of GR, but significantly decreased the amount of heat-shock protein 90 (HSP90) and HSP90-associated GR. Alternatively, TAT activity and TAT mRNA levels increased significantly after the addition of GL to hepatocytes pretreated with DEX. In conclusion, GL reduces the affinity of GRs for ligands through the decreased HSP90 expression, but significantly enhances the glucocorticoid-induced TAT-gene expression at the transcriptional level in rat hepatocytes.