Genotype-specific mechanisms for hepatic steatosis in chronic hepatitis C infection.
BACKGROUND
Hepatic steatosis is common in hepatitis C, but the relative importance of host and viral factors is controversial. In the present prospective study, we examined metabolic factors associated with non-alcoholic fatty liver and viral genotype as predictors of steatosis and fibrosis in chronic hepatitis C infection.


METHODS
In 124 chronic hepatitis C patients, the association between liver histology and the following was investigated: demographic and anthropometric data, alcohol intake, alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglyceride, transferrin saturation, ferritin, insulin, c-peptide, glucose and insulin resistance (homeostasis model).


RESULTS
By multivariate analysis, genotype 3 was associated with increased steatosis grade (P = 0.02). There were significant pairwise interactions between genotype 3 status and total cholesterol (P = 0.01), current alcohol intake (P = 0.04) and serum ALT (P = 0.01). This showed that the etiology of steatosis was different in patients with genotype 3 and those with non-genotype 3 chronic hepatitis C infection. In genotype 3 patients, the degree of steatosis was inversely associated with serum cholesterol (P = 0.005) and positively associated with serum triglyceride (P = 0.02). There was no association between body mass index (BMI) and the extent of steatosis. Among patients with other genotypes, the steatosis grade was strongly influenced by BMI (P < 0.0001) and serum ALT (P < 0.01). Independent predictors of fibrosis were age (P = 0.001), past alcohol intake (P = 0.04), ALT (P = 0.002), serum insulin (P = 0.001) and portal inflammation (P < 0.001).


CONCLUSIONS
Hepatitis C genotype 3 may interfere with pathways of hepatic lipid metabolism, whereas increased BMI appears to be a more important pathogenic factor in other genotypes. Although steatosis and BMI were not associated with hepatic fibrosis, their relationship with serum insulin suggests that metabolic factors related to insulin action could influence fibrogenesis in hepatitis C.
Hui
Jason M
JM
Storr Liver Unit, Westmead Millennium Institute, University of Sydney and Department of Anatomical Pathology, New South Wales, Australia.
Kench
James
J
Farrell
Geoffrey C
GC
Lin
Rita
R
Samarasinghe
Dev
D
Liddle
Christopher
C
Byth
Karen
K
George
Jacob
J
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index