The beneficial effect of aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of cirrhosis

The aim of this study was to examine the effect of the antithrombotic drugs aspirin and enoxaparin on fibrosis progression and regenerative activity in a rat model of liver cirrhosis and to determine if these two drugs are beneficial in animals with advanced fibrosis or with established cirrhosis undergoing partial hepatectomy. Thioacetamide-induced cirrhotic rats received saline (N=10), aspirin (N=7), or enoxaparin (N=11) for a 5-week treatment period. Hepatic fibrosis was assessed according to METAVIR score. Liver regeneration was monitored using PCNA immunostaining. Compared to untreated cirrhotic controls, a significant improvement in fibrosis grade was observed in the aspirin (43%; chi(2) = 54, P < 0.001) and enoxaparin (36%; chi(2) = 43, P < 0.001) treated groups. Postoperatively, total serum bilirubin levels were lower in the aspirin (1.4 +/- 0.18 mg/dl; P < 0.01) and enoxaparin (1.8 +/- 0.35 mg/dl; P < 0.05)-treated groups compared to untreated cirrhotic controls (3.2 +/- 0.6 mg/dl). Hepatic regenerative activity was significantly improved in the aspirin group (57.3%+/- 6.8%, versus 34.2%+/- 7.2% in untreated cirrhotic controls; P < 0.01) but unchanged in the enoxaparin group. We conclude that aspirin and enoxaparin hold promise as a useful therapy for patients with extensive fibrosis.