Whole-body Insulin Resistance is Associated with Elevated Serum α-fetoprotein Levels in Patients with Chronic Hepatitis C

Objective Little is known about the relationship between elevated serum α-fetoprotein (AFP) levels and in- sulin resistance, which adversely influence the clinical course of chronic hepatitis C (CHC). Therefore, we investigated the association between serum AFP and insulin resistance in patients with CHC. Methods We retrospectively investigated 300 patients with CHC without hepatoma who underwent liver bi- opsies and oral glucose tolerance tests. Patients taking antidiabetic drugs were excluded. We analyzed factors associated with elevated AFP levels ( 10.0 ng/mL) in 265 eligible patients. Twenty patients with a homeosta- sis model assessment for insulin resistance value of 2.0 and a whole-body insulin sensitivity index of <5.0 received prospective lifestyle intervention. Results A univariate analysis showed that the body mass index, platelet count, levels of albumin, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase, glucose metabolism, hepatic in- flammation, fibrosis and steatosis were associated with elevated AFP levels. In a multivariate analysis, a platelet count of <15×10 4 /μL, aspartate aminotransferase level of 50 IU/L, γ-glutamyl transpeptidase level of 35 IU/L, whole-body insulin sensitivity index of <5.0 and stage 3-4 fibrosis were independently associated with an elevated AFP level. A Bayesian Network analysis showed that the aspartate aminotransferase level, whole-body insulin sensitivity index and hepatic fibrosis were directly associated with an elevated AFP level. The lifestyle intervention significantly improved the serum AFP level, homeostasis model assessment for in- sulin resistance and whole-body insulin sensitivity index. Conclusion Whole-body insulin resistance is associated with an elevated serum AFP level in patients with CHC. Lifestyle interventions targeting insulin resistance can reduce the serum AFP level and may ameliorate the clinical course of CHC.