56, P < 0.0001; data not shown). In addition, another study has reported that BCAA-enriched supplements ameliorated IR in patients

with chronic liver disease.[26] Although serum BCAA levels were not significantly increased, the serum tyrosine levels decreased after the administration of BCAA-enriched supplements,[26] suggesting that changes in serum tyrosine levels reflect changes in IR. Although it remains unclear how BCAA caused a decrease in tyrosine levels, this result supports our finding that the serum tyrosine levels and IR are correlated. Therefore, the regulation of serum tyrosine concentrations may ameliorate IR in patients with HCV-related chronic liver disease. In addition, serum tyrosine may be associated with suppression of cytokine

signaling 3 (SOCS-3), which contributes to IR, because BCAA suppress Tanespimycin SOCS-3.[27] In addition to serum tyrosine, total cholesterol was a significant independent parameter contributing to IR in the present study. Total cholesterol may be associated with IR because HCV infection and chronic hyperinsulinemia cause disturbances in lipid metabolism.[28, 29] Our study has some limitations. First, we did not evaluate individual amino acids. Because BCAA and AAA have significant associations with future onset of diabetes mellitus,[15, 17] further investigation of the association between individual amino acids and IR is necessary. Second, we were unable to obtain liver specimens for all patients; therefore, we did not include histological findings in the analyses of clinical parameters contributing to IR. Similar studies that include histological findings for all patients should be Selleck SB203580 conducted. In conclusion, serum tyrosine levels may be associated with IR in patients with HCV-related chronic liver disease. Therefore, it may be important to regulate serum tyrosine to control IR in patients with HCV-related chronic liver disease.

We hope that our finding of an association between tyrosine and IR will lead to the discovery of new pathophysiological mechanisms underlying IR. “
“See article in J. Gastroenterol. Hepatol. 2012; 27: 1181–1186. “
“The incidence of liver disease progression among subjects with histologically advanced Carbohydrate but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year.