Survival predictors in patients treated with a molecular adsorbent recirculating system

Table 1 Indications for MARS and treatment protocols

Etiology	MARS treatment initiation criteria	Treatment protocol
ALF	Rapid deterioration of hepatic synthetic function and clinical condition despite standard medical therapy and (one of the following criteria)	Twenty-two hours sessions daily until the native liver recovers
	Ingestion of a lethal dose of a known hepatotoxin (mushroom, paracetamol, iron, etc)	A suitable transplant organ is found
	Patient fulfills the criteria for highly urgent Ltx	Irreversible organ damage occurs
AOCLF	Rapid deterioration of hepatic synthetic function and clinical condition despite standard medical therapy and (two of the following criteria)	Eight hours sessions based on the daily assessment of the surgeon and anesthesiologist until the patient’s clinical condition improves
	Hyperbilirubinemia, bil > 400 &mgr;mol/L	A suitable transplant organ is found
	Hepatorenal syndrome type 1	Irreversible organ damage occurs
	Progressive hepatic encephalopathy (grade ≥ 2)
GF	No set criteria; depends on the assessment of the transplant surgeon and anesthesiologist	No set protocol; based on the daily assessment of the surgeon and anesthesiologist

ALF: Acute liver failure; AOCLF: Acute-on-chronic liver failure; GF: Graft failure.

Table 2 Demographic, clinical, and treatment data at the beginning of MARS treatment

Characteristic	All patients	ALF			AOCLF		Graft failure
		Toxic	Unknown cause	Other	Alcohol-related	Other
Number of patients	192	63	41	9	45	17	11
Age, years	49 (14-81)	41 (14-81)	51 (19-68)	43 (32-58)	52 (30-71)	54 (16-75)	47 (18-62)
Sex, % male (n)	48 (93)	48 (30)	32 (13)	33 (3)	69 (31)	47 (8)	36 (4)
Body mass index, kg/m2	26 (17-56)	24 (17-40)	28 (19-37)	28 (23-34)	27 (18-46)	27 (20-56)	27 (19-56)
MARS sessions/patient	2 (1-13)	2 (1-8)	3 (1-12)	3 (1-9)	2 (1-13)	2 (1-9)	2 (1-4)
Duration of MARS session, h	16.5 (4-22.5)	15.0 (5.5-22)	16.8 (4-22)	16.0 (6.4-22)	20.1 (7.8-22)	18.3 (4.5-22.5)	17.5 (9.5-22)
Mechanically ventilation used, % (n)	36 (69)	29 (18)	34 (14)	56 (5)	29 (13)	41 (7)	73 (8)
Vasoactive-medications used, % (n)	43 (82)	33 (21)	27 (11)	33 (3)	47 (21)	82 (14)	63 (7)
Renal insufficiency, % (n)	49 (94)	33 (21)	37 (15)	44 (4)	60 (27)	76 (13)	73 (8)
MELD score	32 (5-52)	27 (5-48)	32 (23-50)	27 (23-46)	39 (17-52)	36 (27-44)	26 (20-47)
Mean encephalopathy grade before treatment (± SD)	1.8 (1.5)	1.6 (1.6)	2.0 (1.4)	2.4 (1.7)	1.5 (1.4)	1.9 (1.6)	2.0 (1.9)
Mean encephalopathy grade after treatment (± SD)	1.4 (1.6)	1.4 (1.7)	1.5 (1.7)	1.4 (1.6)	1.1 (1.5)	1.9 (1.8)	1.3 (1.7)
P	< 0.001	NS	0.05	0.04	0.02	NS	0.059

All demographic values are expressed as median (range) or percentage of patients (number of patients). Encephalopathy grades are expressed as mean ± SD). NS: Non-significant.

Table 3 Changes in laboratory parameters during MARS treatment in different liver failure subgroups

	Before MARS	After MARS	Percent change	P	Before MARS	After MARS	Percent change	P	Before MARS	After MARS	Percent change	P
	Toxic ALF (n = 63)				Unknown-cause ALF (n = 41)				Other ALF (n = 9)
Hemoglobin g/L	110 (77-170)	100 (59-136)	-9	< 0.001	110 (74-146)	98 (71-134)	-11	0.001	98 (80-131)	88 (82-120)	-10	NS
Leucocytes 109/L	8.6 (1.0-29.2)	8.7 (2.4-33.9)	1	NS	8.9 (2.8-21.9)	8.4 (2.9-42.5)	-6	NS	7.6 (2.6-41)	11.4 (1.7-30.6)	50	NS
Platelets 109/L	130 (11-438)	80 (9-349)	-38	< 0.001	140 (48-511)	74 (25-327)	-47	< 0.001	97 (37-248)	85 (19-184)	-12	0.04
CRP g/L	9 (5-157)	15 (5-186)	67	< 0.001	8 (5-120)	10 (5-142)	25	0.006	30 (5-331)	33 (5-148)	10	NS
Creatinine &mgr;mol/L	79 (35-1318)	51 (17-585)	-35	< 0.001	84 (36-572)	54 (17-337)	-36	< 0.001	85 (57-567)	53 (23-149)	-38	0.02
Urea mmol/L	4.8 (0.8-31.2)	1.7 (0.2-11.7)	-65	< 0.001	6.3 (1.0-25.6)	1.8 (0.8-58)	-71	< 0.001	12.0 (4.2-29.3)	4.3 (1.0-6.7)	-64	0.01
NH4-ion &mgr;mol/L	75 (18-512)	55 (3.5-258)	-26	< 0.001	75 (24-244)	56 (20-309)	-25	0.006	81 (8-317)	45 (17-176)	-45	NS
Bilirubin &mgr;mol/L	84 (4-761)	97 (6-355)	15	0.05	472 (35-725)	301 (10-570)	-36	< 0.001	372 (62-694)	190 (94-348)	-49	NS
AST U/L	842 (15-24360)	282 (15-5240)	-67	< 0.001	427 (50-18140)	183 (19-4080)	-57	< 0.001	600 (37-12640)	83 (43-2227)	-86	NS
ALT U/L	1120 (11-12500)	565 (5-9970)	-50	< 0.001	550 (71-11946)	174 (33-7790)	-68	< 0.001	217 (22-6710)	171 (21-1321)	-21	0.04
γ-GT U/L	72 (8-2139)	55 (9-1279)	-24	0.01	106 (20-503)	49 (5-238)	-54	< 0.001	157 (21-1422)	62 (22-1010)	-61	NS
FV %	33 (5-201)	51 (5-149)	55	0.07	33 (5-119)	23 (7-101)	-33	NS	55 (7-100)	53 (26-127)	-3	NS
AT3 %	44 (15-125)	41 (15-122)	-6	0.002	26 (15-78)	27 (15-68)	4	NS	32 (19-110)	33 (18-92)	3	NS
TT (%)	22 (6-80)	30 (6-112)	36	NS	17 (6-44)	18 (6-68)	3	NS	26.5 (6-53)	36 (16-52)	36	NS
INR	2.5 (1.1-7.7)	2 (1.0-9.9)	-20	NS	3.1 (1.5-9.9)	2.8 (1.5-10)	-10	NS	2.3 (1.4-5.5)	1.8 (1.4-3)	-22	NS
	Alcohol-related AOCLF (n = 45)				Other AOCLF (n = 17)				Graft failure (n = 11)
Hemoglobin g/L	101 (59-129)	94 (75-123)	-7	0.01	96 (71-130)	91 (75-104)	-5	NS	96 (86-117)	99 (71-123)	3	NS
Leucocytes 109/L	17.2 (5-39.3)	16.7 (2.1-45.7)	-3	NS	10 (1.4-30.7)	5.7 (1.3-30)	-43	0.01	9.5 (1.7-14.9)	8.8 (2.1-20.8)	-7	NS
Platelets 109/L	129 (15-508)	83 (6-349)	-36	< 0.001	82 (27-238)	57 (19-215)	-30	0.004	81 (27-453)	83 (16-206)	2	NS
CRP g/L	32 (5-110)	38 (5-160)	19	NS	35 (5-67)	38 (5-110)	9	0.01	22 (6-172)	23 (9-64)	5	NS
Creatinine &mgr;mol/L	167 (49-686)	65 (20-216)	-61	< 0.001	210 (29-325)	52 (17-149)	-75	< 0.001	159 (39-301)	70 (22-121)	-56	0.003
Urea mmol/L	17.5 (1.8-56.5)	3.5 (0.7-18.3)	-80	< 0.001	16.9 (3.2-27.4)	3.1 (1.2-12.3)	-82	< 0.001	16.5 (6.0-32.3)	4.7 (1.3-10.0)	-72	0.004
NH4-ion &mgr;mol/L	73 (12-311)	60 (23-144)	-18	0.05	89 (19-223)	62 (21-96)	-30	0.03	47 (17-177)	32 (25-69)	-32	NS
Bilirubin &mgr;mol/L	513 (17-840)	271 (14-499)	-47	< 0.001	481 (278-909)	283 (134-530)	-41	0.001	311 (107-720)	223 (74-348)	-28	0.009
AST U/L	156 (27-4540)	140 (13-1959)	-10	0.002	210 (31-1230)	144 (58-1222)	-31	0.03	321 (27-12560)	226 (53-87380)	-30	NS
ALT U/L	74 (9-2904)	69 (8-2480)	-7	< 0.001	100 (18-681)	85 (27-286)	-16	0.07	722 (38-9460)	4400 (48-25120)	509	NS
γ-GT U/L	198 (29-1086)	147 (19-810)	-26	< 0.001	69 (19-429)	61 (12-342)	-12	NS	180 (26-2385)	174 (34-1619)	-3	NS
FV %	53 (8-125)	46 (8-131)	-12	< 0.001	34 (7-124)	26 (8-124)	-24	0.005	79 (7-131)	77 (13-107)	-3	NS
AT3 %	34 (13-88)	29 (15-67)	-13	0.001	29 (15-100)	23 (15-100)	-21	0.01	54 (15-137)	56 (17-104)	-4	NS
TT (%)	22 (9-135)	17 (6-49)	-23	0.02	20 (6-96)	17 (6-73)	-15	NS	42 (8-139)	47 (20-113)	-12	NS
INR	2.4 (1.3-5.6)	2.9 (1.3-9.9)	21	0.03	2.4 (1-8.5)	2.9 (1.1-8.5)	21	0.01	1.5 (0.9-6.4)	1.5 (1.0-2.8)	0	NS

All laboratory values are expressed as median (range). NH₄-ion: Ammonium ion (normal range: 36-86 mmol/L); AST: Aspartate aminotransferase; γ-GT: gamma glutamyltransferase; FV: Coagulation factor V (normal range: 80%-120%); AT3: Antithrombin III (normal range 80%-120%); TT (%): Thrombin time (normal range, 70%-130%) (includes coagulation factors II, VII, X).

Table 4 Demographic data, clinical condition, and laboratory parameters before treatment in survivors and non-survivors treated with MARS

	ALF			AOCLF
	Transplant-free survivors	Non-survivors and transplant recipients	P	Transplant-free survivors	Non-survivors and transplant recipients	P
Demographic and clinical data at baseline
Number of patients (n)	54	59		9	53
Age, years (range)	39 (14-81)	50 (19-71)	< 0.0001	52 (30-58)	52 (16-75)	NS
Sex, male % (n)	52 (28)	31 (18)	0.021	67 (6)	62 (33)	NS
BMI, kg/m2	24 (16.9-39.7)	27 (17-40)	NS	32 (18-38)	26 (20-56)	NS
MARS sessions/patient	2 (1-5)	3 (1-12)	< 0.0001	1 (1-3)	2 (1-13)	NS
Mechanical ventilation used % (n)	20 (11)	44 (26)	0.007	33 (3)	32 (17)	NS
Vasoactive-medication used % (n)	28 (15)	34 (20)	NS	33 (3)	60 (32)	NS
Renal insufficiency % (n)	32 (17)	39 (23)	NS	56 (5)	66 (35)	NS
MELD score (range)	24 (5-48)	32 (7-50)	< 0.0001	28 (17-48)	37 (25-52)	0.08
Encephalopathy grade prior to treatment	0 (0-4)	3 (0-4)	< 0.0001	1 (0-4)	1 (0-4)	NS
Laboratory values at baseline
Hemoglobin g/L	113 (78-170)	106 (74-160)	NS	106 (80-127)	99 (59-130)	NS
Leucocytes 109/L	8.3 (1-23.4)	9.1 (2.6-41)	0.045	9.7 (1.4-35.3)	15.5 (1.6-39.3)	NS
Platelets 109/L	146 (11-351)	130 (37-511)	NS	131 (69-383)	107 (15-508)	NS
CRP g/L	10 (5-331)	8 (5-153)	NS	28 (8-58)	35 (5-110)	NS
Creatinine &mgr;mol/L	77 (35-1318)	91 (36-567)	NS	128 (56-556)	210 (29-686)	NS
Urea mmol/L	5.2 (1.1-31.2)	7.8 (0.8-29.3)	NS	8.4 (2.3-39.6)	17.45 (1.8-56.5)	NS
NH4-ion &mgr;mol/L	50 (8-512)	99 (24-389)	< 0.0001	66 (12-241)	75 (19-311)	NS
Bilirubin &mgr;mol/L	71 (4-761)	425 (8-694)	< 0.0001	455 (17-745)	514 (143-909)	NS
AST U/L	732 (15-24 360)	497 (50-20900)	NS	214 (27-2030)	164 (31-4540)	NS
ALT U/L	1165 (11-12 500)	708 (71-10 890)	NS	69 (9-2904)	87 (10-897)	NS
γ-GT U/L	61 (8-503)	109.5 (20-2139)	0.013	230 (44-398)	109 (19-1086)	NS
FV %	51 (7-201)	31 (5-101)	0.012	65 (41-124)	48 (7-125)	0.028
AT3 %	52 (15-125)	27 (15-110)	< 0.0001	40 (15-100)	29.5 (13-88)	0.043
TT (%)	26 (6-80)	16 (6-49)	< 0.0001	26 (9-96)	21 (6-135)	NS
INR	2.3 (1.1-7.7)	3.2 (1.4-9.9)	< 0.0001	2 (1-4.3)	2.4 (1-8.5)	NS
Albumin g/L	29.9 (19.2-46.4)	24.8 (11.5-41.2)	< 0.0001	23.3 (13.6-31.8)	21.8 (14.7-32.7)	NS