Lack of Association between Hepatitis C Virus core Gene Variation 70/91aa and Insulin Resistance

Abstract

The role of hepatitis C virus (HCV) in insulin resistance (IR) is not fully understood. The aim of this study was to determine the impact of amino acid (aa) substitutions in the core region of HCV according to IR and to identify clinical and laboratory associations. Ninety-two treatment-naive HCV patients were recruited to determine laboratory data and blood cell count. IR was determined using Homeostasis Model Assessment (HOMA) index where IR was defined as HOMA ≥2. HCV RNA load and genotype were determined by Abbott Real time HCV. HCV core region was determined by direct nucleotide sequencing. Bivariate analysis was conducted using HOMA IR ≥2 as a dependent factor. IR prevalence was 43.5% (n = 40), vitamin D sufficiency was found in 76.1% (n = 70) and 72.8% (n = 67) had advanced liver fibrosis. In the bivariate analyses, elevated values of γGT (p = 0.024) and fibrosis staging (p = 0.004) were associated with IR, but IR was not related to core mutations. The presence of glutamine in position 70 was associated with low vitamin D concentration (p = 0.005). In the multivariate analysis, no variable was independently associated with HOMA-IR. In conclusion, lack of association between IR and HCV core mutations in positions 70 and 91 suggests that genetic variability of this region has little impact on IR.

Metabolic Factors and Their Influence on the Clinical Course and Response to HCV Treatment

“…Mutation at core 70Q have been associated to higher incidence of HCC and mutations in 70 and/or 91 core HCV are important predictors of IR in patients without cirrhosis or DM [13,14]. However, this finding was not seen in Brazilian population [12].…”

“…HCV core protein is involved in the development of IR, however little is known about the clinical impact of HCV core region on IR [11,12]. Patients infected with HCV genotype 1b who had 70Q core mutation had higher rates of IR compared to those without the mutation, indicating that this substitution is associated with the development of IR [11].…”

Before Direct-Acting Antivirals for Hepatitis C Virus: Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV

“…HCV modulates hepatic glucose metabolism by impairing insulin signaling and glucose uptake [ 29 ]. This substitution is related to the presence of insulin resistance (IR) and glucose intolerance, mainly in Asian individuals, although a lack of association with IR has been reported in Brazilian patients [ 12 , 30 , 31 , 32 ].…”