Efficacy of recombinant human thrombopoietin in patients with acute-on-chronic liver failure and thrombocytopenia: A prospective, open-label study

Table 1 Baseline patients characteristics at enrollment, n (%)

	rhTPO (n = 35)	Control (n = 35)	P value1
Demographic
Sex			0.057
Male	32 (91.4)	26 (74.3)
Female	3 (8.6)	9 (25.7)
Age, mean ± SD, year	53.5 ± 10.9	50.1 ± 12.1	0.214
Etiology
Alcoholic liver disease	16 (45.7)	9 (25.7)	0.073
Hepatitis B	16 (45.7)	26 (74.3)
Hepatitis C	1 (2.9)	0 (0)
Non-alcoholic steatohepatitis	1 (2.9)	0 (0)
Autoimmune liver disease	1 (2.9)	0 (0)
Cirrhosis	26 (74.2)	21 (60.0)	0.203
Laboratory findings, median (Q1-Q3)
WBC, 109/L	2.5 (1.9, 5.3)	4.8 (3.1, 8.2)	< 0.001
Hemoglobin, g/L	108.0 (78.0, 121.0)	113.5 (98.0, 124.0)	0.228
Neutrophil, %	70.8 (63.5, 79.0)	78.7 (67.3, 87.2)	0.055
Platelet count, 109/L	28.0 (19.0, 39.0)	35.0 (24.0, 42.0)	0.130
Albumin, g/L	28.2 (24.4, 31.7)	27.5 (22.8, 31.8)	0.742
Alanine transaminase, U/L	34.0 (20.0, 71.0)	64.0 (35.0, 148.0)	0.003
Aspartate transaminase, U/L	59.0 (36.0, 106.0)	82.0 (45.0, 173.0)	0.152
Alkaline phosphatase, U/L	110.0 (88.0, 161.0)	70.5 (44.0, 140.0)	0.037
Gamma-glutamyl transferase, U/L	47.0 (22.0, 138.0)	113.0 (56.0, 212.0)	0.023
Total bilirubin, μmol/L	88.8 (76.3, 144.1)	113.9 (95.2, 132.7)	0.053
Creatinine, μmol/L	72.0 (59.0, 93.7)	64.0 (52.0, 81.0)	0.095
INR	1.7 (1.5, 2.1)	2.1 (2.0, 2.6)	0.088
MELD	17.0 (9.0, 22.0)	18.0 (13.8, 23.0)	0.187

¹P value indicates the comparison of variables between recombinant human thrombopoietin group and control group.

WBC: White blood cell count; INR: International normalized ratio; MELD: Model for end-stage liver disease; rhTPO: Recombinant human thrombopoietin.

Table 2 Dynamic changes in serum platelet count and white blood cell levels in the recombinant human thrombopoietin and control groups, n (%)

Variables	rhTPO (n = 35)	Control (n = 35)	P value1
The proportion of patients with platelet count > 50 × 109/L on day 14
Baseline	3 (8.6)	2 (5.7)	1.000
Day 7	8 (22.9)	8 (27.6)	0.664
Day 14	17 (60.7)	3 (12.0)	< 0.001
Platelet count, 109/L
Baseline	28 (19, 39)	35 (24, 42)	0.213
Day 7	34 (20, 50)a	37 (27, 53)a	0.274
Day 7 change from baseline	3.0 (-3.0, 18.0)	3.0 (-2.5, 26.5)	0.956
Day 14	64 (33, 91)a	33 (24, 42)	0.005
Day 14 change from baseline	24.5 (4.0, 47.0)	0 (-11.0, 13.0)	< 0.001
WBC, 109/L
Baseline	2.5 (1.9, 5.3)	4.8 (3.1, 8.2)	< 0.001
Day 7	3.0 (2.2, 4.4)	4.5 (2.9, 6.8)	0.016
Day 7 change from baseline	0.21 (-0.45, 0.80)	-0.22 (-2.27, 0.49)	0.275
Day 14	4.0 (2.3, 5.4)	3.3 (2.6, 5.3)a	0.695
Day 14 change from baseline	0.11 (-0.90, 2.24)	-0.67 (-2.14, 0.00)	0.019

^aP < 0.05 indicates statistically significant differences comparing with baseline.

¹P value indicates the comparison of variables between recombinant human thrombopoietin group and control group.

Values are expressed as median. rhTPO: Recombinant human thrombopoietin; WBC: White blood cell count.

Table 3 Dynamic changes in liver function and coagulation parameters in the recombinant human thrombopoietin and control groups

Variables	rhTPO (n = 35)	Control (n = 35)	P value1
Alanine transaminase, U/L
Baseline	34.0 (20.0, 71.0)	64.0 (35.0, 148.0)	0.003
Day 7	27.0 (18.0, 36.0)a	46.0 (22.0, 72.5)a	0.009
Day 7 change from baseline	-8 (-22, -3)	-18 (-50.5, -6.5)	0.050
Day 14	26.0 (15.0, 41.0)a	35.0 (18.0, 53.0)a	0.346
Day 14 change from baseline	-9 (-33, 3)	-19.5 (-61, -8)	0.063
Aspartate transaminase, U/L
Baseline	59.0 (36.0, 106.0)	82.0 (45.0, 173.0)	0.152
Day 7	42.0 (30.0, 71.0)a	57.0 (31.0, 97.0)a	0.209
Day 7 change from baseline	-17 (-36, -2)	-20 (-141, 0)	0.398
Day 14	49.0 (27.0, 71.0)a	46.0 (27.0, 56.0)a	0.678
Day 14 change from baseline	-21.5 (-34, 3)	-46 (-106, -15)	0.056
Albumin, g/L
Baseline	28.2 (24.4, 31.7)	27.5 (22.8, 31.8)	0.742
Day 7	29.6 (26.0, 32.1)a	29.8 (26.5, 32.0)a	1.000
Day 7 change from baseline	1.7 (-1.0, 4.2)	2.9 (-2.0, 6.7)	0.611
Day 14	32.6 (29.3, 35.3)a	31.7 (26.3, 33.8)a	0.318
Day 14 change from baseline	4.9 (0.8, 8.6)	4.0 (0.0, 6.6)	0.323
Total bilirubin, μmol/L
Baseline	88.8 (76.3, 144.1)	113.9 (95.2, 132.7)	0.053
Day 7	91.8 (51.5, 138.9)a	105.3 (84.3, 119.8)	0.143
Day 7 change from baseline	-12.5 (-41.8, 6.7)	-10.5 (-31.1, 9.7)	0.787
Day 14	82.4 (49.9, 154.7)	86.2 (61.1, 121.1)a	0.920
Day 14 change from baseline	-29.0 (-43.1, 9.0)	-25.6 (-51.6, -4.9)	0.681
MELD
Baseline	17 (9.0, 22)	18 (13.8, 23)	0.187
Day 7	15 (8.5, 18.5)	16 (13, 19)	0.230
Day 7 change from baseline	-1 (-3, 1)	-1 (-5, 1)	0.791
Day 14	15 (10.5, 16.5)a	15 (11, 21)	0.087
Day 14 change from baseline	-2 (-6.5, 0)	-2 (-5, 1)	0.676
INR
Baseline	1.7 (1.5, 2.1)	2.1 (2.0, 2.6)	0.088
Day 7	1.7 (1.5, 2.0)a	2.0 (1.7, 2.2)a	0.017
Day 7 change from baseline	-0.085 (-0.330, 0.030)	-0.140 (-0.575, 0.055)	0.493
Day 14	1.5 (1.4, 1.8)a	2.0 (1.8, 2.3)	< 0.001
Day 14 change from baseline	-0.22 (-0.34, -0.08)	-0.105 (-0.450, 0.035)	0.293

^aP < 0.05 indicates statistically significant differences comparing with baseline.

¹P value indicates the comparison of variables between recombinant human thrombopoietin group and control group.

Values are expressed as median (Q1-Q3). rhTPO: Recombinant human thrombopoietin; MELD: Model for end-stage liver disease; INR: International normalized ratio.

Table 4 The adverse reactions, bleeding events and prognosis, n (%)

	rhTPO (n = 35)	Control (n = 35)	P value
Fever	2 (6.7)	2 (6.7)	1.000
Thrombophilia	0	0	1.000
Bleeding events	4 (11.4)	8 (22.9)	0.205
Death	3 (8.6)	6 (17.1)	0.284

rhTPO: Recombinant human thrombopoietin.