Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China

doi:10.3748/wjg.v28.i27.3503

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World Journal of Gastroenterology

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Retrospective Study

World J Gastroenterol. Jul 21, 2022; 28(27): 3503-3513
Published online Jul 21, 2022. doi: 10.3748/wjg.v28.i27.3503

Table 1 Clinical and biochemical data of examined patients

Parameter	Training cohort (n = 296)¹	Validation cohort (n = 211)¹	P value
Age (yr)	42.47 ± 11.98	41.21 ± 11.36	0.167
Gender: Female/male (n)	75/221	40/171	0.091
Drinking: Yes/no (n)	127/169	101/110	0.268
Smoking: Yes/no (n)	92/204	68/143	0.784
HbeAg: Negative/positive	16/280	15/196	0.430
Fibrosis stage: F0/F1/F2/F3/F4	55/58/75/64/44	47/47/37/54/26	0.194
Activity grade: A0/A1/A2/A3/A4	16/92/113/69/6	15/72/69/52/3	0.446
WBC (× 10⁹/L)	5.89 ± 2.55	6.34 ± 4.32	0.150
NEUT × 10⁹/L)	3.55 ± 2.44	3.66 ± 2.61	0.611
LYMPH (× 10⁹/L)	1.72 ± 0.62	1.80 ± 0.63	0.063
PLT (× 10⁹/L)	171.61 ± 66.87	174.48 ± 61.62	0.636
Albumin (g/L)	41.12 ± 19.09	39.94 ± 6.07	0.380
Globulin (g/L)	29.67 ± 5.45	29.14 ± 5.80	0.298
TBIL (μmol/L)	16.51 ± 8.44	16.73 ± 7.63	0.768
DBIL (μmol/L)	6.91 ± 5.03	7.07 ± 4.33	0.699
ALT (U/L)	73.31 ± 65.41	96.85 ± 83.62	0.002
AST (U/L)	72.59 ± 63.29	77.44 ± 67.34	0.411
ALP (U/L)	97.70 ± 41.98	104.32 ± 49.25	0.104
γ-GT (U/L)	85.64 ± 69.68	97.98 ± 75.36	0.058
AGPR	1.26 ± 0.84	1.32 ± 0.89	0.431

¹Data presented as the mean ± SD or proportions.

HbeAg: Hepatitis B e-antigen; WBC: White blood cell; NEUT: Neutrophil count; LYMPH: Lymphocyte count; PLT: Platelet; TBIL: Total bilirubin; DBIL: Direct bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; γ-GT: Gamma-glutamyl transpeptidase; AGPR: [Alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)]/platelet (10⁹/L).

Table 2 Univariate analysis in the training cohort

Parameter	Fibrosis (F0-1) (n = 113)¹	Fibrosis (F2-4) (n = 183)¹	P value
Age (yr)	45.15 ± 14.97	43.63 ± 13.32	0.363
Gender: Female/male (n)	37/76	38/145	0.021
WBC (× 10⁹/L)	6.45 ± 3.02	5.55 ± 2.14	0.003
NEUT (× 10⁹/L)	4.14 ± 3.0	3.18 ± 1.95	0.001
LYMPH (× 10⁹/L)	1.67 ± 0.60	1.68 ± 0.63	0.828
PLT (× 10⁹/L)	206.0 ± 68.39	150.55 ± 56.49	< 0.001
Albumin (g/L)	41.26 ± 5.93	39.29 ± 5.66	0.005
Globulin (g/L)	27.46 ± 4.46	31.04 ± 5.56	< 0.001
TBIL (μmol/L)	13.82 ± 7.06	17.12 ± 8.8	< 0.001
DBIL (μmol/L)	6.43 ± 3.72	7.81 ± 4.49	< 0.001
ALT (U/L)	65.01 ± 70.72	78.42 ± 66.62	0.101
AST (U/L)	56.61 ± 55.11	82.45 ± 66.09	0.001
ALP (U/L)	79.06 ± 34.16	109.2 ± 42.31	< 0.001
γ-GT (U/L)	51.84 ± 47.06	106.5 ± 73.21	< 0.001
AGPR	0.72 ± 0.49	1.61 ± 0.83	< 0.001

¹Data presented as the mean ± SD or proportions.

WBC: White blood cell; NEUT: Neutrophil count; LYMPH: Lymphocyte count; PLT: Platelet; TBIL: Total bilirubin; DBIL: Direct bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; γ-GT: Gamma-glutamyl transpeptidase; AGPR: [Alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)]/platelet (10⁹/L).

Table 3 Comparisons of the receiver operating characteristic curve between different non-invasive indices

	Training cohort (n = 296)						Validation cohort (n = 211)
	F0-1 vs F2-4		F0-2 vs F3-4		F0-3 vs F4		F0-1 vs F2-4		F0-2 vs F3-4			F0-3 vs F4
AGPR
AUROC (95%CI)	0.83 (0.78-0.87)		0.84 (0.79-0.88)		0.87 (0.83-0.91)		0.83 (0.77-0.88)		0.83 (0.77-0.89)			0.84 (0.78-0.89)
Cut-off values	0.87		1.20		1.40		0.87		1.20			1.40
Se/Sp (%)	83.1/73.4		72.22/80.3		88.6/75.4		85.5/68.1		78.7/70.2			92.3/67.0
PPV/NPV (%)	83.5/72.8		67.8/83.4		38.6/97.4		76.9/79.0		61.8/84.4			28.2/98.4
Positive/negative LR	3.13/0.23		3.67/0.35		3.60/0.15		2.68/0.21		2.65/0.30			2.80/0.11
HR (95%CI)	8.48 (5.22-14.33)		7.56 (4.76-9.83)		8.10 (5.11-11.63)		8.02 (4.95-15.62)		7.06 (4.51-12.35)			5.06 (3.89-7.72)
GPR
AUROC (95%CI)	0.77 (0.72-0.82)		0.81 (0.76-0.85)		0.80 (0.75-0.84)		0.80 (0.74-0.85)		0.81 (0.74-0.87)			0.78 (0.71-0.83)
Cut-off values	0.32		0.32		0.56		0.32		0.32			0.56
Se/Sp (%)	73.7/70.8		76.8/54.8		79.5/65.9		86.3/67.0		91.2/56.5			75.0/62.3
PPV/NPV (%)	80.4/62.5		49.4/80.5		28.9/94.9		76.5/79.7		56.2/91.4			26.5/86.9
Positive/negative LR	2.53/0.37		1.70/0.42		2.33/0.31		2.62/0.20		2.10/0.15			1.95/0.41
HR (95%CI)	6.53 (4.81-9.62)		6.72 (3.96-9.63)		6.47 (4.08-9.83)		6.45 (3.58-11.61)		7.30 (3.87-14.62)			4.84 (3.28-7.95)
APRI
AUROC (95%CI)	0.72 (0.67-0.77)		0.70 (0.64-0.75)		0.76 (0.70-0.81)		0.76 (0.70-0.82)		0.74 (0.67-0.82)			0.77 (0.70-0.83)
Cut-off values	0.5	1.5	-		1.0	2.0	0.5	1.5	-	1.0		2.0
Se/Sp (%)	80.9/58.4	36.1/79.7	-		77.3/64.7	43.2/83.3	83.8/54.3	34.1/76.6	-	70.1/68.6		50.1/78.3
PPV/NPV (%)	75.9/65.3	74.2/43.5	-		27.6/94.2	31.1/89.4	69.5/72.9	64.5/48.3	-	26.3/92.7		30.8/91.9
Positive/negative LR	1.94/0.33	1.77/0.80	-		2.19/0.35	2.59/0.68	1.83/0.30	1.46/0.86	-	2.12/0.44		3.16/0.63
HR (95%CI)	2.61 (1.85-3.67)		1.85 (1.41-2.42)		2.09 (1.63-2.55)		1.59 (1.23-2.07)		2.64 (1.76-4.32)			2.13 (1.71-2.58)
FIB-4
AUROC (95%CI)	0.74 (0.69-0.79)		0.75 (0.69-0.80)		0.80 (0.75-0.84)		0.74 (0.67-0.80)		0.79 (0.73-0.84)			0.77 (0.71-0.83)
Cut-off values	-		1.45	3.25	-		-		1.45		3.25	-
Se/Sp (%)	-		87.9/47.3	42.6/87.2	-		-		77.5/58.1		37.5/93.1	-
PPV/NPV (%)	-		49.0/87.3	65.7/72.6	-		-		53.0/80.9		76.9/70.9	-
Positive/negative LR	-		1.67/0.25	3.34/0.66	-		-		1.85/0.39		5.46/0.67	-
HR (95%CI)	1.86 (1.52-2.53)		1.94 (1.55-2.42)		2.17 (1.77-2.56)		1.98 (1.50-2.62)		2.11 (1.63-2.74)			1.87 (1.68-2.36)
Comparison of AUROC
AGPR and GPR	P = 0.008		P < 0.0001		P = 0.0001		P = 0.028		P = 0.005			P = 0.0008
AGPR and APRI	P < 0.0001		P < 0.0001		P = 0.0002		P = 0.0001		P = 0.0001			P = 0.134
AGPR and FIB-4	P = 0.0004		P = 0.0005		P = 0.022		P = 0.007		P = 0.174			P = 0.100
GPR and APRI	P = 0.0007		P = 0.0028		P = 0.284		P = 0.003		P = 0.016			P = 0.831
GPR and FIB-4	P = 0.026		P = 0.331		P = 0.922		P = 0.093		P = 0.929			P = 0.591
APRI and FIB-4	P = 0.455		P = 0.028		P = 0.061		P = 0.248		P = 0.008			P = 0.795

AGPR: [Alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)]/platelet count (10⁹/L); AUROC: Area under the receiver operating characteristic curve; Se: Sensitivity; Sp: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; LR: Likelihood ratio; HR: Hazard ratio; CI: Confidence interval; GPR: Gamma-glutamyl transpeptidase to platelet ratio; APRI: Aspartate aminotransferase-to-platelet ratio index; FIB-4: Age (years) × aspartate aminotransferase (U/L)/[platelet (10⁹/L) × alanine aminotransferase (U/L)^1/2].

Citation: Liao MJ, Li J, Dang W, Chen DB, Qin WY, Chen P, Zhao BG, Ren LY, Xu TF, Chen HS, Liao WJ. Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China. World J Gastroenterol 2022; 28(27): 3503-3513
URL: https://www.wjgnet.com/1007-9327/full/v28/i27/3503.htm
DOI: https://dx.doi.org/10.3748/wjg.v28.i27.3503