Abstract
BackgroundIn chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV).MethodsTwo hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G⁄T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses.ResultsThe most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G⁄T SNP in patients infected with HCV genotype 3 (P < 0.001).ConclusionsIn chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels.
Highlights
In chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment
The multivariate analysis of a cohort of 239 Brazilian patients chronically infected with hepatitis C virus (HCV) showed that the GT/the mutated allele (TT) genotype of the microsomal triglyceride transfer protein (MTTP) -493G/T single-nucleotide polymorphisms (SNPs) was associated with hepatic steatosis in patients infected with HCV genotype 3, in a total cohort of 239 Brazilian patients chronically infected with HCV, including 198 patients infected with HCV genotype non-3 and 41 infected with HCV genotype 3
We identified an association between hepatic steatosis and inflammatory activity in patients infected with HCV, which is consistent with the results of Leandro et al [25], who conducted a robust analysis of 3068 patients contained in 10 databases and concluded that steatosis was associated with fibrosis in patients with chronic hepatitis C via inflammatory reactions because hepatic inflammation can promote fibrogenesis in patients with hepatic steatosis
Summary
In chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment [3]. Hepatic steatosis is a metabolic factor characterized by an accumulation of triglycerides in hepatocytes, and this disorder has a significant impact on the progression of liver fibrosis. Genetic determinants of hepatic steatosis are observed such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene and patatin-like phospholipase-3 (PNPLA3) gene [5, 7]
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