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

Abstract

Objective Little is known about the relationship between elevated serum α-fetoprotein (AFP) levels and insulin 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 biopsies 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 homeostasis 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 inflammation, 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 insulin 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.

Successful Hepatitis C Antiviral Therapy Induces Remission of Type 2 Diabetes: A Case Report

“…Although type 2 diabetes and insulin resistance have been identified as risk factors for the progression of liver fibrosis and development of hepatocellular carcinoma, the mechanism by which this occurs is not clear [ 9 – 12 ]. The relationship between AFP and insulin resistance was recently examined in a retrospective analysis of 300 HCV-infected patients [ 30 ]. This study demonstrated that whole-body insulin resistance and hepatic fibrosis correlated directly with elevated levels of AFP.…”

Alpha-Fetoprotein (AFP) and Inflammation: Is AFP an Acute and/or Chronic Phase Reactant?

“…This report revealed that elevated AFP levels were associated with age, fibrosis, histologically observed inflammation, abnormal liver enzymes, and total bilirubin levels. A second study involving HCV also showed that elevated AFP concentrations correlated with low platelet counts, reduced albumin levels, decreased liver enzymes, fibrosis, and insulin resistance [59]. In comparison to the above, HBV infected patients also displayed elevated AFP levels (2,000 ng/mL), while AFP levels in patients of HBV combined with liver cancer showed AFP increases of 10-fold (20,000 ng/mL) [60].…”

Impact of Body Weight Reduction via Diet and Exercise on the Anti-Viral Effects of Pegylated Interferon Plus Ribavirin in Chronic Hepatitis C Patients with Insulin Resistance: A Randomized Controlled Pilot Trial

“…The results presented here suggest that metabolic factors may be a major cause of IR in CHC patients. Because hyperinsulinemia or hyperglycemia due to IR can cause hepatic fibrosis (1) or hepatocarcinogenesis (17)(18)(19), lifestyle interventions may improve the prognosis of HCV-infected patients.…”