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Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis.

Abstract：

BACKGROUND & AIMS: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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Mirandola S,Realdon S,Iqbal J,Gerotto M,Dal Pero F,Bortoletto G,Marcolongo M,Vario A,Datz C,Hussain MM,Alberti A

doi

10.1053/j.gastro.2006.02.035

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

1661-9

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(06)00391-X

journal_volume

130

pub_type

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Liver microsomal triglyceride transfer protein is involved in hepatitis C liver steatosis.