title: Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis.
abstract: OBJECTIVE
  Hepatic steatosis is frequent in chronic hepatitis C. Several mechanisms might be implicated, including metabolic cofactors and direct viral effects on intracellular lipid pathways. In a transgenic mouse model, hepatitis C virus (HCV) was shown to inhibit microsomal triglyceride transfer protein (MTP) activity, which is essential for hepatic lipoprotein assembly and secretion. No data are available on liver MTP activity in HCV-infected patients. We therefore investigated liver MTP gene expression and its lipid transfer activity in untreated cases infected with the major HCV genotypes showing variable degrees of hepatic steatosis.
  
  
  METHODS
  MTP messenger RNA (mRNA) levels were measured by real-time polymerase chain reaction, and MTP activity was assessed by fluorescent assay in liver biopsy specimens of 58 HCV-positive patients. A set of metabolic and serum lipid markers was also measured at the time of liver biopsies.
  
  
  RESULTS
  MTP mRNA levels showed a statistically significant (P = .001) inverse correlation with the degree of steatosis, independently of the HCV genotype. MTP mRNA levels also had an inverse correlation with serum insulin (P = .0002), homeostasis model assessment-insulin resistance (HOMA-IR) (P = .005), and body mass index (P = .02) in patients with HCV-1 and HCV-2 and with serum HCV-RNA (P = .02) in HCV-3 patients. Liver MTP-specific activity was significantly reduced in HCV-3 patients compared with those with other HCV genotypes (P = .004) and correlated with reduced serum cholesterol, apo B, and low-density lipoproteins.
  
  
  CONCLUSIONS
  MTP may play a central role in HCV-related steatosis, being modulated by different genotype-specific mechanisms, mainly hyperinsulinemia in non-HCV-3 patients, and more profound and direct virus-related effects in HCV-3-infected individuals.
authors.affiliation: VIMM-Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mirandola
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.forename: Jahangir
authors.initials: J
authors.lastname: Iqbal
authors.forename: Martina
authors.initials: M
authors.lastname: Gerotto
authors.forename: Francesca
authors.initials: F
authors.lastname: Dal Pero
authors.forename: Gladis
authors.initials: G
authors.lastname: Bortoletto
authors.forename: Moira
authors.initials: M
authors.lastname: Marcolongo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vario
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
authors.forename: Alfredo
authors.initials: A
authors.lastname: Alberti
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001483:Base Sequence; D001707:Biopsy, Needle; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000401:mortality / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011336:Probability; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; D012333:RNA, Messenger; C106092:microsomal triglyceride transfer protein