Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis c virus genotype 1.
Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild <30%, or moderate-severe > or =30%. Thirty nondiabetic, nonobese blood donors served as controls. RBP4 levels were measured by a human competitive enzyme-linked immunosorbent assay kit (AdipoGen). Mean values of RBP4 were similar in NAFLD and CHC (35.3 +/- 9.3 microg/L versus 36.8 +/- 17.6; P = 0.47, respectively), and both were significantly higher than in controls (28.9 +/- 12.1; P = 0.02 and P = 0.01, respectively). RBP4 was higher in CHC patients with steatosis than in NAFLD (42.1 +/- 19.7 versus 35.2 +/- 9.3; P = 0.04). By linear regression, RBP4 was independently linked to steatosis only (P = 0.008) in CHC, and to elevated body mass index (P = 0.01) and low grading (P = 0.04) in NAFLD. By linear regression, steatosis was independently linked to homeostasis model assessment score (P = 0.03) and high RBP4 (P = 0.003) in CHC. By logistic regression, RBP4 was the only variable independently associated with moderate-severe steatosis in CHC (odds ratio, 1.045; 95% confidence interval, 1.020 to 1.070; P = 0.0004), whereas waist circumference was associated with moderate-severe steatosis in NAFLD (odds ratio, 1.095; 95% confidence interval, 1.007 to 1.192; P = 0.03).


CONCLUSIONS
In nondiabetic, nonobese patients with genotype 1 CHC, serum RBP4 levels might be the expression of a virus-linked pathway to steatosis, largely unrelated to IR.
Cattedra ed Unità Operativa di Gastroenterologia, University of Palermo, Palermo, Italy.
Salvatore
S
Petta
Calogero
C
Cammà
Vito
V
Di Marco
Nicola
N
Alessi
Francesco
F
Barbaria
Daniela
D
Cabibi
Rosalia
R
Caldarella
Stefania
S
Ciminnisi
Anna
A
Licata
Maria Fatima
MF
Massenti
Alessandra
A
Mazzola
Giuseppe
G
Tarantino
Giulio
G
Marchesini
Antonio
A
Craxì
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005234:Fatty Liver / Q000097:blood* / Q000209:etiology / Q000473:pathology / Q000821:virology*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism*; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma