Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis.
OBJECTIVE
To explore the influence of polymorphisms in genes encoding for the chemokines Stromal cell-Derived Factor-1 (SDF-1)/CXCL12 and Monocyte Chemotactic Protein-1 (MCP-1)/CCL2, or for the chemokine receptor CCR5 on the risks of liver-related death and hepatocellular carcinoma (HCC) occurrence in hepatitis C virus (HCV)-infected patients.


METHODS
SDF-1 3'A, MCP-1 (-2518) and CCR5-Delta32 polymorphisms, SDF-1 alpha, Regulated upon Activation Normal T cells Expressed and Secreted (RANTES)/CCL5 and MCP-1 serum levels were determined in 120 HCV-infected patients, included at time of cirrhosis diagnosis and prospectively followed-up.


RESULTS
During follow-up, 23/120 (19.1%) patients died and 47/120 (39.1%) developed HCC. Carriers and noncarriers of each genetic marker had similar baseline characteristics estimating the severity of liver disease. The occurrence of death or HCC during follow-up was similar among carriers and noncarriers of each polymorphism. There was no association between the carriage of mutated alleles and chemokine serum levels and the latter were not associated with the risks of death or HCC.


CONCLUSIONS
This study suggests the lack of association of SDF-1 3'A, MCP-1 (-2518), CCR5-Delta32 polymorphisms with death and HCC occurrence in cirrhotic HCV-infected patients.
Nahon
Pierre
P
Department of Hepatology, Jean Verdier Hospital AP-HP, Service d'Hepatologie Hospital Jean Verdier Avenue du 14 Juillet, Bondy 93140, France. pierre.nahon@jvr.aphp.fr
Sutton
Angela
A
Rufat
Pierre
P
Simon
Chantal
C
Trinchet
Jean-Claude
JC
Gattegno
Liliane
L
Beaugrand
Michel
M
Charnaux
Nathalie
N
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000821:virology; D018932:Chemokine CCL2 / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000235:genetics / Q000276:immunology / Q000401:mortality; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics*; D016019:Survival Analysis
C111835:CCL2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D019713:Receptors, CCR5