Hepatocyte steatosis in patients infected with genotype 1 hepatitis C virus.
BACKGROUND
Recent findings suggest a higher prevalence of hepatic steatosis in patients with chronic hepatitis C, estimated at 50%. Both host and viral factors contribute to the development of steatosis in chronic hepatitis C. Steatosis is an initial stage, which promotes hepatic fibrosis through oxidative stress.


OBJECTIVE
To assess the pathogenic mechanism of genotype 1 hepatitis C virus in steatosis and to evaluate the correlation between the degree of steatosis and the level of oxidative stress.


METHODS
The study was carried out on 50 patients (29 males, 21 females) with genotype 1 HCV and liver biopsy proven chronic hepatitis C. Patients with other etiology of chronic liver disease were excluded. We statistically correlated the degree of steatosis with clinical (age, sex, waist circumferences) and biological parameters (alaninaminotransferase, gammaglutamyltranspeptidase - GGT, insulin, ferritin, serum viral load, oxidative stress). Insulin resistance (IR) was determined by the homeostasis model assessment (HOMA) method. The oxidative stress was estimated by serum malondialdehyde (MDA) and glutathione (GSH).


RESULTS
27 patients presented steatosis (57%): 14 out of 29 men (48%) and 14 out of 21 women (66%); in two thirds of them, steatosis was moderate. Univariate analysis identified five parameters that significantly influenced steatosis: age >45 years, sex - female, IR (HOMA>2.5), BMI, central adiposity (as reflected by waist circumferences and high GGT-values). Multivariate analysis identified four significant parameters: sex - female, insulin resistance (HOMA>2.5), BMI>30 kg/m(2) and GGT>2N. No relationship was found between steatosis and viral replication. The study demonstrated a significant correlation between steatosis and IR on the one hand and between steatosis and liver fibrosis on the other hand (p<0.05). Liver fibrosis was significant correlated with the increase levels of free radicals (MDA>250 nmol/dL).


CONCLUSIONS
The pathogenic mechanism of genotype 1 HCV in steatosis is independent from viral replication and it may be linked to virus induced metabolic abnormalities such as IR. More women (66%) than men (48%) developed steatosis. Increased levels of free radicals, correlated with moderate and severe steatosis suggest the intervention of oxidative stress in determining the hepatic lesions associated with steatosis.
Fierbinţeanu-Braticevici
Carmen
C
2nd Medical Clinic - Gastroenterology, University Hospital Bucharest, Romania. cfierbinteanu@yahoo.com
Mohora
Maria
M
Tribus
Laura
L
Petrişor
Ana
A
Creţoiu
Sanda M
SM
Creţoiu
D
D
Usvat
R
R
Ioniţă
L
L
D005234:Fatty Liver / Q000378:metabolism / Q000821:virology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress