Increased fibrosis progression rates in hepatitis C patients carrying the prothrombin G20210A mutation

Table 1 Patient characteristics by fibrosis rates (by Poynard)

	Slow fibrosers	Fast fibrosers	P value
	(n = 116)	(n = 52)
Female (%)	37%	31%	0.43
Age (yr)	49.8 ± 10.5	43.9 ± 7.1	< 0.001
Age at infection (yr)	25.1 ± 10.8	25.2 ± 7.7	0.97
Infection duration (yr)	24.7 ± 8	18.7 ± 8.1	< 0.001
Alcohol intake ≥ 50 g/d	7.1%	10.4%	0.53
BMI (kg/m2)	23.8 ± 2.9	23.4 ± 3.1	0.5
Genotype (%)			0.49
1	74.3%	62.8%
2	2.8%	2.3%
3	16.5%	23.3%
4	6.4%	11.6%
Inflammatory score, grade (units)	1.3 ± 0.68	1.81 ± 0.69	< 0.001
Fibrosis stage (%)			< 0.001
0	14.7%	0%
1	45.7%	9.6%
2	29.3%	5.8%
3	8.6%	48.1%
4	1.7%	36.5%

BMI: Body mass index.

Table 2 Frequency of hypercoagulation mutations (%)

Mutation type	Wild type	Heterozygote	Homozygote
Factor V Leiden (n = 159)	96.2	3.8	0
Prothrombin 20210 (n = 156)	92.3	7.1	0.6
MTHFR (n = 163)	35.6	50.9	13.5

Percentages of patients carrying each of the mutations by genotype. MTHFR: Methylene tetrahydrofolate reductase.

Table 3 Percentage of hypercoagulation gene mutation carriage by rate of fibrosis (by Poynard)

Gene	Mutation carriage	Percent of slow fibrosers	Percent of fast fibrosers	P value
PT20210	Wild type	94.5	86.9	0.181
	Heterozygote	5.5	10.9
	Homozygote	0	2.2
Factor V Leiden	Wild type	95.5	98	0.67
	Heterozygote	4.5	2
	Homozygote	0	0
MTHFR	Wild type	35.6	36	0.80
	Heterozygote	52	48
	Homozygote	12.4	16

¹Heterozygote and homozygote categories were unified for Fisher's exact test. PT20210: Prothrombin 20210; MTHFR: Methylene tetrahydrofolate reductase.

Table 4 Prothrombin 20210 mutation rates in various “fibrosis rate” models

Rate of fibrosis	PT20210 mutation in slow fibrosers (%)	PT20210 mutation in fast fibrosers (%)	P value3
Rate of fibrosis by Poynard	5.50	13	0.18
0.13 units/yr1	5.10	15.80	0.07
0.133 units/yr2	5	16.70	0.03

Various cut-offs of rate of fibrosis were employed on our cohort to differentiate between fast and slow fibrosers.

¹Rate of fibrosis according to Fishman et al[22];

²Rate of fibrosis according to Wright et al[10];

³P value calculated by Fisher’s exact test. PT20210: Prothrombin 20210.

Table 5 Linear regression analysis of rate of fibrosis

Predictive variable	R2	P value
PT20210 status	0.093	0.002
Age	0.022	0.033
Gender	0.016	0.042
Age of infection	0.167	< 0.001
BMI	Not contributing
Alcohol consumption	Not contributing
Inflammation grade	0.121	< 0.001

PT20210: Prothrombin 20210; BMI: Body mass index.

Table 6 Multivariate analysis of the association between rate of liver fibrosis (slow fibrosers vs fast fibrosers) predicted by prothrombin 20210 mutation and various known parameters

Parameter	OR (95% CI)	P-wald1
Age	0.91 (0.86-0.96)	< 0.001
PT20210	4.76 (1.13-19.99)	0.033
Inflammation grade2	7.42 (3.07-17.95)	< 0.001

Variables removed from the model: gender, BMI and alcohol consumption.

¹The Wald test was used to assess the significance of each logit;

²Inflammation was categorized: grades 0 and 1 compared with grades 2 and 3. PT20210: Prothrombin 20210; OR: Odds ratio; CI: Confidence interval.