Effects of Anticoagulants on Experimental Models of Established Chronic Liver Diseases: A Systematic Review and Meta-Analysis

Table 1

Characteristics of included studies.

Study	Study design	Animals	Animal number	Modeling method	Treatment groups	Main outcomes	Courses
Kassel et al. [12]	Unclear	C57BL/6	Unclear	Western diet (40% kcal from milk fat), NAFLD	Vehicle pumps and argatroban pumps	Antifibrotic effect	23 weeks
Li et al. [13]	Unclear	Sprague-Dawley rats	52	CCl4/porcine serum, hepatic fibrosis	Normal control, CCl4, porcine serum, CCl4 + LAAH, and porcine serum + LAAH	Liver function tests, and area of collagens	10 weeks
Lee et al. [16]	Unclear	Sprague-Dawley rats	24	1% DMN, hepatic fibrosis	Control, DMN, DMN + LH, and DMN + LHP	Antifibrotic effect	4 weeks
Vilaseca et al. [17]	Randomized controlled study	Wistar rats, Sprague-Dawley rats	Unclear	CCl4/TAA, cirrhosis	Rivaroxaban and vehicle	Antifibrotic effects, HSC activation, and portal pressure	18 weeks
Cerini et al. [21]	Randomized controlled study	Wistar rats and Sprague-Dawley rats	Unclear	CCl4/TAA, cirrhosis	Enoxaparin and vehicle	Antifibrotic effect and inflammation response	15 weeks
Fortea et al. [22]	Unclear	Sprague-Dawley rats	Unclear	CCl4, cirrhosis	Saline, CCl4 + Saline, and CCl4 + enoxaparin	Survival, liver function tests, antifibrotic effect, and inflammation response	12 weeks
Assy et al. [28]	Unclear	Sprague-Dawley rats	28	TAA, hepatic cirrhosis	Controls, aspirin, and enoxaparin	Survival, liver function tests, and antifibrotic effect fibrosis	5 weeks
Li et al. [29]	Randomized controlled study	Sprague-Dawley rats	45	TAA, hepatic fibrosis	TAA, TAA + low-dose aspirin, TAA + high-dose aspirin, and TAA + enoxaparin	Liver function tests and antifibrotic effect	4 weeks
Yan et al. [30]	Randomized controlled study	C57BL/6	Unclear	CCl4, cirrhosis	Different groups of the enzymatically depolymerized heparins and saline	Liver function tests, antifibrotic effect, and inflammation response	8 weeks
Fujita et al. [31]	Randomized controlled study	Fischer rats	344	A CDAA diet or an HF/HC diet, NAFLD	CDAA, CDAA + aspirin, CDAA + ticlopidine, CDAA + cilostazol, CSAA	Antifibrotic effect and inflammation response	16 weeks
Abdel-Salam et al. [32]	Randomized controlled study	Sprague-Dawley rats	48	Bile duct ligated (BDL), cholestatic liver injury	Sham, BDL, BDL + UFH, BDL + nadroparin, BDL + tinzaparin, and BDL + enoxaparin	Liver function tests	3 weeks
Abe et al. [33]	Unclear	Wistar rats	Unclear	CCl4, hepatic fibrosis	CCl4 and CCl4 + dalteparin	Antifibrotic effect	7 weeks
Lee et al. [34]	Unclear	Sprague-Dawley rats	24	TAA, hepatic fibrosis	Saline, and dabigatran etexilate	Liver function tests, antifibrotic effect, fibrin deposition, intrahepatic angiogenesis, and portal hypertension	12 weeks
Mahmoud et al. [35]	Randomized controlled study	Albino rats	24	CCl4, hepatic fibrosis	Control group, CCl4, and CCl4 + rivaroxaban	Liver function tests, antifibrotic effect, and inflammation response	6 weeks
Mahmoud et al. [36]	Randomized controlled study	Albino rats	56	CCl4, hepatic fibrosis	Normal control, fibrosis control, dabigatran-treated, and clopidogrel-treated group	Liver function tests, antifibrotic effect, and inflammation response	6 weeks
Liu et al. [37]	Unclear	Sprague-Dawley rats	27	CCl4, hepatic fibrosis	Control group, CCl4, and CCl4 + aspirin	Liver function tests, antifibrotic effect, and inflammation response	6 weeks

ATIII, antithrombin III; BDL, bile duct ligated; CDAA, choline-deficient, L-amino acid-defined; CCl₄, carbon tetrachloride; CSAA, choline-sufficient l-amino acid; HF/HC, high-fat high-calorie; L-amino acid-defined; DMN, dimethylnitrosamine; LAAH, low anticoagulant activity heparin; LH, low molecular weight heparin; LHP, low molecular weight heparinepluronic nanogel; NAFLD, nonalcoholic fatty liver disease; TAA, thioacetamide; UFH, unfractionated heparin.