Multicenter clinical study on Fuzhenghuayu capsule against liver fibrosis due to chronic hepatitis B

Table 1 General information in two groups before treatment (mean±SD).

Group	n	Sex M/F	Age (yr)	Marriage single/married	Weight (kg)	Previous treatment(case)	Treated withother drugs (case)
Experimental	110	95/15	37.7±9.2	21/89	64.30±8.25	11	26
Control	106	89/17	38.5±8.9	15/91	64.09±6.64	17	26
P		0.848	0.512	0.361	0.844	0.155	0.174

Table 2 Blood and renal routine and PT in two groups before treatment (mean±SD).

Group	n	RBC (1012/L)	Hemoglobin (g/L)	WBC (109/L)	Platelet (109/L)	BUN (mmol/L)	Cr (mmol/L)	PT (s)
Experimental	110	4.6±0.7	139.8±16.7	5.1±1.4	137.1±86.0	4.4±1.3	84.1±17.4	13.6±1.9
Control	106	4.5±0.7	138.9±16.5	5.0±1.4	117.8±48.1	4.7±1.6	86.9±21.0	13.5±1.7
P		0.499	0.761	0.499	0.054	0.193	0.441	0.168

PT: prothrombin time, BUN: blood urea nitrogen, Cr: creatinine.

Table 3 Inflammation grading and fibrosis staging of biopsies in two groups before treatment.

Group	n	Inflammation (G)				Fibrosis (S)
		1	2	3	4	1	2	3	4
Experimental	99	12	49	29	9	22	39	21	17
Control	96	22	39	27	8	33	31	20	12
P		0.277				0.121

Table 4 Serum viral markers in two groups (cases) before treatment.

Group	n	HBsAg	HBsAb	HBeAg	HBeAb	HBcAb	HBcAb-IM	HBV-DNA
Experimental	110	110	3	48	48	105	40	38
Control	106	106	2	48	56	100	35	37
P			1.000	0.891	0.220	0.765	0.659	1.000

Table 5 Comparison of inflammation activity (G) in two groups in liver biopsy.

Group	n	Pretreatment					Post-treatment					P
		1	2	3	4	mean	1	2	3	4	mean
Experimental	50	5	25	15	5	2.40	18	20	11	1	1.9	0.001
Control	43	10	19	12	2	2.14	11	17	10	5	2.21	0.583
P		0.277					0.004

Table 6 Comparison of liver fibrosis staging (S) in two groups in liver biopsy.

Group	n	Pretreatment						After treatment						P
		0	1	2	3	4	mean	0	1	2	3	4	mean
Experimental	50	0	8	23	10	9	2.40	1	23	14	9	3	1.80	0.001
Control	43	0	11	20	7	5	2.14	2	8	22	4	7	2.14	1.000
P		0.121						0.001

Table 7 Inflammation activity scoring in liver biopsy before and after treatment (mean±SD).

Group	n	Pretreatment	Post-treatment	P
Experimental	37	8.8±3.9	6.6±4.7	0.001
Control	31	7.3±4.1	7.4±4.1	0.978
P		0.185 (P1)	0.036 (P2)

Table 8 Fibrosis scoring in liver biopsy before and after treatment (mean±SD).

Group	n	Pretreatment	Post-treatment	P
Experimental	37	8.1±5.6	6.0±5.4	0.001
Control	31	7.2±5.5	8.1±6.3	0.413
P		0.433 (P1)	0.007 (P2)

Table 9 Efficacy in two groups in histologic changes of liver fibrosis.

Group	n	Very effective cases (%)	Effective cases (%)	Ineffective cases (%)	P
Experimental	50	4 (8.0)	22 (44.0)	24 (48.0)
					0.008
Control	43	1 (2.4)	9 (20.9)	33 (76.7)

Table 10 Changes in serum HA, LM, P-III-P and IV-C contents (mean±SD).

Parameter	Group	n	Pretreatment	12 wk of treatment	24 wk of treatment
HA (mg/L)	Experimental	110	303.6±235.7	178.9±158.0b	147.9±131.3b
	Control	106	276.3±234.9	258.9±243.2a	261.8±253.6b
LM (mg/L)	Trial	110	137.0±84.6	127.5±92.7a	122.4±96.5b
	Control	106	134.1±98.6	128.4±55.7	121.2±48.9
P-III-P (mg/L)	Experimental	110	11.1±5.0	8.8±4.9b	7.4±4.4b
	Control	106	9.6±5.6	9.7±6.6	9.4±6.9
IV-C (mg/L)	Trial	110	119.1±132.5	74.5±88.4b	64.5±82.5b
	Control	106	91.8±76.7	71.4±57.8	62.4±54.7b

^aP<0.05,

^bP<0.01 vs the same group.

Table 11 Difference in serum HA, LM, P-III-P and IV-C contents between two groups before and after treatment.

Time points	Group	n	HA (mg/L)			LM (mg/L)
			Median of difference	Standard deviation	Percent of difference	Median of difference	Standard deviation	Percent of difference
12-wk treatment	Experimental	110	-75.6b	196.5	-36.3	-10.0a	58.3	-8.1
	Control	106	-19.8	222.6	-12.8	3.0	102.2	2.0
24-wk treatment	Experimental	110	-96.1b	201.5	-48.5	-17.0	69.3	-13
	Control	106	-26.0	254.6	-15.9	-4.5	108.0	-4.5

^aP<0.05,

^bP<0.01 vs control.

Table 12 Changes in serum P-III-P, IV-C contents between two groups before and after treatment.

Time points	Group	n	P-III-P (mg/L)			IV-C (mg/L)
			Median of differential	Standard deviation	Percent of difference	Median of difference	Standard deviation	Percent of difference
12-wk treatment	Experimental	110	-2.2b	5.0	-20.1	-25.0a	128.2	-39.3
	Control	106	-0.0	5.0	-1.3	-6.5	87.0	-9.1
24-wk treatment	Experimental	110	-2.9b	4.6	-33.9	-33.0a	139.1	-48.3
	Control	106	-0.3	5.5	-3.0	-14.0	80.4	-18.6

^aP<0.05,

^bP<0.01 vs control.

Table 13 Efficacy on liver fibrosis in two groups.

Group	n	Very effective cases (%)	Effective cases (%)	Ineffective cases (%)	P
Experimental	110	80 (72.7)	2 (1.8)	28 (25.5)
					0.001
Control	106	29 (27.4)	2 (1.9)	75 (70.7)

Central effect-oriented CMH method was employed in comparison of efficacy between two groups, Q of statistics was Q_CMH.

Table 14 Changes in liver function of two groups before and after treatment (mean±SD).

Parameter	Group	Pretreatment	6 wk of treatment	12 wk of treatment	18 wk of treatment	24 wk of treatment
Alb (g/L)	Experimental	40.1±5.2	42.6±5.0b	43.2±4.7b	43.3±4.3bc	43.5±5.7bc
	Control	41.0±5.9	42.6±5.3b	43.3±5.3b	42.8±4.9b	43.1±5.2b
Glo (g/L)	Experimental	30.1±6.4	29.8±6.1	30.8±6.5	31.3±5.7	31.3±5.8
	Control	29.2±5.1	30.9±5.7b	30.9±6.0a	31.9±5.6b	31.9±6.6b
ALT (U/L)	Experimental	116.0±74.6	57.5±56.0bc	50.9±39.0bc	50.1±43.6bc	49.4±41.2bc
	Control	96.7±55.0	59.5±52.0b	58.9±54.4b	61.8±58.5b	51.2±39.0b
AST (U/L)	Experimental	78.4±59.3	55.5±47.7b	54.2±47.4b	46.2±29.2bc	48.2±35.0b
	Control	68.5±53.1	53.8±39.1b	59.3±50.2a	55.8±39.4a	51.9±51.6b
GGT (U/L)	Experimental	92.0±71.4	75.3±64.9b	67.9±75.8b	67.4±70.1b	56.4±51.8bd
	Control	86.8±68.6	68.6±52.9b	67.7±59.9b	70.4±48.0a	67.3±58. 2b
ALP (U/L)	Experimental	100.6±38.2	96.4±47.3a	100.3±52.2	97.9±47.1	93.5±38.8a
	Control	95.1±41.9	97.0±43.6	93.1±42.1	91.1±36.5	92.9±41.5
TBil (mmol/L)	Experimental	17.8±7.9	15.8±5.9b	15.9±6.4b	15.5±9.5bc	15.5±5.8bc
	Control	16.9±8.4	16.4±8.2	17.1±8.6	18.5±12.1	18.5±13.5
DBil (mmol/L)	Experimental	5.9±5.5	4.7±3.0b	4.6±3.0bc	4.5±2.5bc	4.6±2.7bd
	Control	5.2±4.4	4.8±3.7	5.1±3.7	5.3±3.6	5.9±5.4

^aP<0.05,

^bP<0.01 vs the same group;

^cP<0.05,

^dP<0.01 vs difference between different time points value and previous treatment in two groups.

Table 15 Efficacy in ALT activity between two groups before and after treatment.

Group	n	Effectual (%)	Effective (%)	Noneffective (%)	P
Experimental	110	64 (58.2)	16 (14.5)	30 (27.3)	0.105
Control	106	54 (50.9)	9 (8.5)	43 (40.6)

In comparison of efficacy between two groups, central effect-oriented CMH method was employed. Q of statistics was Q_CMH.

Table 16 Changes in diameter of stem hepatic portal vein, thickness of spleen and diameter of splenic vein before and after treatment in two groups (mean±SD).

Parameters	Group	n	Pretreatment	12-wk treatment	24-wk treatment
Diameter of stem	Experimental	110	12.34±1.94	11.96±1.69bd	12.03±1.61a
hepatic vein (mm)	Control	106	12.30±1.75	12.37±1.76	12.06±1.51
Diameter of	Experimental	110	42.77±9.23	41.10±8.11b	41.77±7.88
spleen (mm)	Control	106	42.45±9.94	42.12±9.90	41.32±8.28a
Diameter of	Experimental	110	7.57±1.86	7.41±1.84	7.28±1.52a
splenic vein (mm)	Control	106	7.67±1.94	7.43±1.80a	7.39±2.00a

^aP<0.05,

^bP<0.01 vs treatment,

^dP<0.01 vs different time point and pretreatment between groups.

Table 17 Comparison of stable rate (%) between two groups in follow up.

Group	Stable cases/follow up cases (stable rate%)
	HA	LM	P-III-P	IV-C	ALT
Experimental	18/29 (62.07)	29/34 (85.29)	14/29 (48.28)	30/34 (88.24)	49/50 (98.00)
Control	16/28 (57.14)	25/37 (67.57)	15/25 (60.00)	34/37 (91.89)	54/54 (100.00)
P	0.790	0.100	0.425	0.703	0.481

Fisher precise probability calculation was employed in comparison of stable rates between the two groups.