Evaluation of hyaluronic acid and type III procollagen peptide as predictors for treatment response to direct-acting antivirals

Table 1 Patients’ characteristics, mean ± SD

Variables	Non-responder	Responder	P value
Gender (male/female)	30/45	40/60	0.242
Age (years)	51.55 ± 6.99	49.4 ± 7.0	0.071
Alanine aminotransaminase (U/L)	70.2 ± 21.0	60.0± 15.8	0.017
Aspartate aminotransaminase (U/L)	68.9 ± 16.9	54.6 ± 14.9	0.004
ALP (U/L)	123.9 ± 32.8	98.9 ± 20.9	0.018
Bilirubin (mg/dL)	1.15 ± 0.28	0.96 ± 0.35	0.011
Albumin (g/dL)	3.35 ± 0.39	3.88 ± 0.51	0.0001
Creatinine (mg/dL)	0.87 ± 0.18	0.81 ± 0.16	0.082
α-fetoprotein (ng/mL)	3.62 ± 1.19	3.59 ± 0.88	0.769
INR	1.25 ± 0.15	1.13 ± 0.06	0.069
Hemoglobin (g/dL)	11.88 ± 2.60	13.10 ± 1.34	0.071
Platelets (× 109/L)	155.9 ± 43.9	191.2 ± 35.9	0.0001
White blood cells (× 109/L)	4.91 ± 1.67	5.49 ± 1.37	0.0620
Red blood cells (× 1012/L)	5.33 ± 1.88	4.98 ± 1.17	0.0840
APRI	1.20 ± 0.31	0.78 ± 0.22	0.0001
FIB-4	3.11 ± 1.01	1.94 ± 0.56	0.0001

P < 0.05 was significant.

ALP: Alkaline phosphatase; INR: international normalized ratio; APRI: Aspartate aminotransferase-platelet ratio index; FIB-4: Fibrosis-4 score.

Table 2 Diagnostic performances of the index compared to each marker alone

Categories	AUC (95%CI)	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	Accuracy (%)
PIIINP ≥ 19.5 μg/L	0.684 (0.59-0.78)	69.3	50	51.0	68.5	58.3
HA ≥ 82 μg/L	0.766 (0.66-0.87)	70.7	69	63.1	75.8	69.71
PIIINP × HA > 1840	0.809 (0.72-0.90)	74.7	74	68.3	79.6	74.3

Cut-off values were obtained from receiver operating characteristic curve analysis. Non-responder patients were compared to responder patients. PIIINP: Type III procollagen N-peptide; HA: Hyaluronic acid; AUC: Area under the receiver operating characteristic curve; PPV: Positive predictive value; NPV: Negative predictive value; CI: Confidence interval.

Table 3 Correlation between the index and each marker alone with factors related to treatment failure

Variable	HA × PIIINP		HA		PIIINP
	r	P value	r	P value	r	P value
ALT (U/L)	0.182	0.091	0.127	0.096	0.121	0.210
AST (U/L)	0.212	0.089a	0.114	0.133	0.150	0.182
ALP (U/L)	0.191	0.059	0.112	0.214	0.071	0.261
Albumin (g/dL)	-0.26	0.021a	-0.20	0.044a	-0.201	0.043a
Bilirubin (mg/dL)	0.194	0.062	0.136	0.079	0.099	0.223
Platelets (× 109/L)	-0.19	0.058	-0.13	0.083	-0.123	0.158
FIB-4	0.216	0.022a	0.186	0.041a	0.185	0.041a
APRI	0.223	0.019a	0.188	0.041a	0.181	0.041a

^aP < 0.05 was significant.

Pearson correlation coefficients were measured for linear relationships. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; FIB-4: Fibrosis-4 score; APRI: Aspartate aminotransferase-platelet ratio index; PIIINP: Type III procollagen N-peptide; HA: Hyaluronic acid.