Genetic and acquired thrombotic factors in chronic hepatitis C.
OBJECTIVE
During the progression of chronic liver disease towards cirrhosis, morphological studies have shown a close association between parenchymal remodeling and obliterative lesions of intrahepatic small portal and hepatic veins. These lesions are highly suggestive of intrahepatic thrombotic events, which may have a key role in the pathogenesis of hepatic fibrosis. The aim of the study was to investigate thrombotic risk factors in chronic hepatitis C patients with different extent of liver fibrosis.


METHODS
The following thrombotic factors were evaluated in 68 hepatitis C patients with prothrombin activity >/= 80% (34 consecutive patients with extensive fibrosis and/or cirrhosis compared with 34 consecutive patients without extensive fibrosis and/or cirrhosis): factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C and S deficiencies, hyperhomocysteinemia, elevated factor VIII level, and lupus anticoagulant.


RESULTS
Three thrombotic risk factors were significantly more frequent in patients with extensive fibrosis and/or cirrhosis than in those without extensive fibrosis: protein C deficiency present in 14 patients (41%) as compared with three patients (9%), p= 0.004; elevated factor VIII level present in 19 patients (56%) as compared with six patients (18%), p= 0.002; and hyperhomocysteinemia present in 10 patients (29%) as compared with two patients (6%), p= 0.023. The association of two or three prothrombotic factors was present in 19 patients (56%) with extensive fibrosis and/or cirrhosis as compared with one patient (3%) without extensive fibrosis and/or cirrhosis, p < 0.001.


CONCLUSIONS
Multiple thrombotic risk factors coexist frequently in patients with extensive fibrosis and early stage of cirrhosis. Their association with local inflammation could favor thrombotic events in the liver micro-circulatory bed.
Poujol-Robert
Armelle
A
Service d'Immunologie et Hématologie Biologiques, Hôpital Saint-Antoine Assistance Publique-Hôpitaux de Paris, Paris, France.
Rosmorduc
Olivier
O
Serfaty
Lawrence
L
Coulet
Florence
F
Poupon
Raoul
R
Robert
Annie
A
D000328:Adult; D000368:Aged; D000991:Antithrombins / Q000032:analysis; D005169:Factor VIII / Q000032:analysis; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000209:etiology / Q000235:genetics*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000150:complications / Q000235:genetics*
D000991:Antithrombins; D011486:Protein C; D017293:Protein S; D006710:Homocysteine; D005169:Factor VIII