Association between thrombotic risk factors and extent of fibrosis in patients with non-alcoholic fatty liver diseases

Table 1 Clinical, biochemical, and demographic characteristics of study population (mean±SD, n)

Characteristics	FL n = 15	NASH n = 15	CH n = 14	Healthy controls n = 10	P
Age (yr)	50±11	53±9	40±13	39±7	0.01
Gender (M/F)	10M/5F	7M/8F	11M/3F	6M/4F	NS
BMI	32±5	33.0±6	24.0±3	25.0±4	0.001
IRI	4.0±3.3	4.7±2.4	1.7±0.9	1.8±0.4	0.001
Hb (g/dL)	14±1.0	14±2.0	14±1.0	13.9±1.0	NS
WBC (×103 cell/mm3)	6.2±1.4	7.4±1.9	7.2±2.1	5.9±0.9	NS
Platelets (103 cell/mm3)	245±49	247±57	226±44	279±72	NS
INR	0.9±0.08	0.9±0.08	0.9±0.09	0.9±0.05	NS
PTT (s)	32±5.0	32±4.0	31.0±4.0	33.0±6.0	NS
Fibrinogen (mg/dL)	336±69	326±57	296±49	291±69	NS
ALT (IU/mL)	45±21	43±18	79±25	20±1.0	0.001
AST (IU/mL)	36±16	35±8	83±8	20±1.0	0.001
ALKPH (IU/mL)	87±22	87±26	73±20	70±1.0	NS
GGT (IU/mL)	73±35	56±29	62±45	50±1.0	0.5
Activity grade	2.1±1.3	8.7±2.5 (3.9)1	10.4±5.1 (12)1	ND	0.01
Fibrosis stage	0.5±0.0	1.4±1.6 (0.5)1	1.5±1.6(1.0)1	ND	NS

¹Numbers in parenthesis represent the median value.

Table 2 Prevalence of thrombotic risk factors in 44 patients of study population (n, %)

Thrombotic risk factors	NAFLD (%)	CH (%)	Total (%)
Protein C deficiency	1 (3)	1 (7)	2 (10)
Protein S deficiency	2 (6)	3 (21)	5 (27)
Anti-thrombin III
deficiency	2 (6)	0 (0)	2 (6)
Lupus anticoagulant	2 (6)	1 (7)	3 (13)
APC resistance	3 (10)	2 (14)	5 (24)
PT20210A mutation	None	None	None
Factor V Leiden	None	None	None
MTHFR mutation	1 (3)1	None	1 (3)

¹Heterozygous mutation.

Table 3 Number of thrombotic risk factors per patient in patients with NAFLD with mild and severe fibrosis score (n)

Number of thromboticrisk factors per patientfibrosis (%)	Mildfibrosis(%)	Severe
No risk factors	8 (47)	1 (6)
One risk factor	4 (23)	3 (18)
Two risk factors	1 (6)	0 (0)

Table 4 Levels of thrombophilic and coagulation factors in all study population (mean±SD)

Factors	FL n = 15	NASH n = 15	CH n = 14	Healthy controls n = 10	P ANOVA
Protein C (%)a	150±34	130±37	101±24	121±12	0.001
(normal 70-130)
Protein S (%)b	106±20	92±19	95±37	90±17	0.01
(normal 60-140)
Anti-thrombin III (%)	115±11	108±17	110±10	116±10	NS
(normal 80-120)
APC ratio	2.2±0.1	2.2±0.9	2.2±0.3	2.2±0.1	NS
(normal >2.0)
Lupus anticoagulant	1.0±0.1	1.05±0.1	1.0±0.1	1.0±0.1	NS
(normal <1.2 U/mL)
Fibrinogen	336±69	326±57	296±49	291±69	NS
(normal 200-400 mg/dL)

¹P = 0.07, FL vs NASH; bP<0.01, FL vs NASH.

Table 5 Clinical and biochemical characteristics in all study population in relation to their fibrosis staging (mean±SD)

Characteristics	NAFLD		CH
	Normal-mildfibrosis	Moderate-severefibrosis	Normal-mildfibrosis	Moderate-severefibrosis
IRI	3.9±3.0	3.9±1.6	1.2±0.7	1.9±0.8
BMI	31±5.0	34±6.7	23.6±1.5	24±3.9
Protein C (%)	128±40	129±36	96±14b	88±13
Protein S (%)	100±22d	84±16	96±19	77±16
Antithrombin III	110±17	116±8.9	111±3.7	101±7.4
APC ratio	2.3±0.1	2.2±0.1	2.01±0.3	2.3±0.3
Lupus anticoagulant	1.0±0.09	1.0±0.09	0.99±0.4	0.99±0.8
PT (%)	105±13	107±13	103±22	97±10
PTT (s)	32±5	29.5±2.0	32±4.6	30±4.3
Fibrinogen, mg/dL	306±57	337±57	290±29	314±64
PT mutation 20210A	Normal	Normal	Normal	Normal
Factor V Leiden	Normal	Normal	Normal	Normal
MTHFR (n)	One mutation	Normal	Normal	Normal
Platelets	244±43	237±47	242±36	225±44
Activity score	5.5±4.2	7.5±2.3	8.0±5.0	12.8±4.3

^aP<0.01, CH mild fibrosis vs CH severe fibrosis;

^bP<0.01, NAFLD mild fibrosis vs NAFLD severe fibrosis.

Table 6 Results of capacity of combined risk factors for thrombosis (protein S, anti-thrombin III, and fibrinogen) in predicting the presence of FL or NASH patients (outcome)¹

Results/	Actual number	Predicted group
LNB	of patients	NASH (%)	FL(%)
NASH	15	11 (73)	4 (27)
FL	15	5 (33)	10 (67)

70% of the cases were classified correctly.