In:
Liver International, Wiley, Vol. 38, No. 1 ( 2018-01), p. 102-112
Abstract:
Recent studies suggest that heparins reduce liver fibrosis and the risk of decompensation of liver disease. Here, we evaluated the effects of enoxaparin in several experimental models of advanced cirrhosis. Methods Cirrhosis was induced in male Sprague‐Dawley ( SD ) rats by: (i) Oral gavage with carbon tetrachloride ( CC l4 ORAL ), (ii) Bile duct ligation ( BDL ) and (iii) CC l4 inhalation ( CC l4 INH ). Rats received saline or enoxaparin s.c. (40 IU /Kg/d or 180 IU /Kg/d) following various protocols. Blood biochemical parameters, liver fibrosis, endothelium‐ and fibrosis‐related genes, portal pressure, splenomegaly, bacterial translocation, systemic inflammation and survival were evaluated. Endothelial dysfunction was assessed by in situ bivascular liver perfusions. Results Enoxaparin did not ameliorate liver function, liver fibrosis, profibrogenic gene expression, portal hypertension, splenomegaly, ascites development and infection, serum IL ‐6 levels or survival in rats with CC l4 ORAL or BDL ‐induced cirrhosis. Contrarily, enoxaparin worsened portal pressure in BDL rats and decreased survival in CC l4 ORAL rats. In CC l4 INH rats, enoxaparin had no effects on hepatic endothelial dysfunction, except for correcting the hepatic arterial dysfunction when enoxaparin was started with the CC l4 exposure. In these rats, however, enoxaparin increased liver fibrosis and the absolute values of portal venous and sinusoidal resistance. Conclusions Our results do not support a role of enoxaparin for improving liver fibrosis, portal hypertension or endothelial dysfunction in active disease at advanced stages of cirrhosis. These disease‐related factors and the possibility of a limited therapeutic window should be considered in future studies evaluating the use of anticoagulants in cirrhosis.
Type of Medium:
Online Resource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2018.38.issue-1
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2124684-1
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