PROGNOSTIC FACTORS OF LIVER TRANSPLANTATION FOR ACUTE-ON-CHRONIC LIVER FAILURE

Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population.

AIM:

Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT.

METHODS:

Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes.

RESULTS:

The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall.

CONCLUSIONS:

LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.

HEADINGS
Liver Transplantation; Liver Cirrhosis; Liver Failure, Acute; Gastroenterology; Survival

Numerical demographic variables for non-parametric distribution
			Hazard ratio [95%CI]

	Total=25 (100%)	Mean±SD	Median+IQR
Age	-	52.9 (±10.29)	-
MELD	-	-	32 (±13)
MELD Na	-	-	32 (±13)
Albumin	-	-	2.8 [IQR_{p 25–75}=2,45–3.5]
Sodium	-	-	139.36 [±4]
INR	-	-	2.5 [IQR_{p 25–75}=1.82–3.035]
Total bilirubin	-	-	5.6 [IQR_{p 25–75}=2–23.8]
V factor (1ºPO)	-	-	66 [IQR_{p 25–75}=35–311.25]
Numerical demographic variables for parametric distribution

	Total=25 (100%)	Yes	No
Male gender		11 (44%)
Number of failing organs/systems		1 organ=11 patients 2 organs=2 patients ≥3 organs=12 patients
Encephalopathy score (%)		Grade I=10 (40) Grade II=05 (20) Grade III=05 (20) Grade IV=02 (08) No encephalopathy=03 (12)
Child-Pugh (%)		A–0 (0) B–03 (12) C–22 (88)
ACLF grade (%)		Grade 1–09 (36) Grade 2–08 (32) Grade 3–08 (32)
Mechanical ventilation pre-LT		6 (24%)
ACLF triggering factor, SBP		11 (44%)
Ascites		24 (96%)
HCV etiology		17 (68%)
ALBI		Grade I=3 patients Grade II=5 patients Grade III=17 patients
Pre-LT sepsis		10 (40%)
Dialysis		14 (56%)
Vasoactive drugs		9 (36%)

	Hazard ratio [95%CI]	p-value
Age	0.660 [0.201–2.164]	0.493
Male gender	0.979 [0.264–3.661]	0.979
MELD	1.029 [0.933–1.136]	0.565
MELD Na	1.034 [0.931–1.159]	0.528
HCV Etiology	0.657 [0.191–2.257]	0.504
Total bilirubin	1.004 [0.974–1.029]	0.761
INR	0.987 [0.924–1.056]	0.711
Sodium	1.078 [0.924–1.056]	0.339
Creatinine	0.885 [0.974–1.029]	0.579
ALBI	3.062 [0.658–14.242]	0.154
Serum albumin level	0.849 [0.405–1.778]	0.664
Pre-LT sepsis	0.993 [0.302–3.270]	0.991
Pre-LT dialysis	0.431 [0.130–1.428]	0.164
Pre-LT mechanical ventilation	1.331 [0.352–5.038]	0.673
Pre-LT vasoactive drug use	0.686 [0.181–2.595]	0.579
SBP as a triggering factor	0.526 [0.153–1.802]	0.308
Number of failing organs/systems	1.154 [0.790–1.688]	0.459
CLIF-OF	1.010 [0.831–1.228]	0.917
CLIF-C ACLF score	1.012 [0.949–1.080]	0.711

	Hazard ratio [95%CI]	p-value
Age	1.005 [0.938–1.078]	0.880
Male gender	0.982 [0.264–3.661]	0.979
MELD	0.968 [0.879–1.067]	0.513
MELD Na	0.965 [0.875–1.065]	0.484
HCV etiology	0.513 [0.137–1.923]	0.322
Total bilirubin	1.013 [1.001–1.025]	0.027
INR	1.009 [1.002–1.016]	0.012
Sodium	1.063 [0.899–1.256]	0.474
ALBI	4.683 [0.585–37.499]	0.146
Seruim albumin	1.131 [1.003–1.276]	0.045
Pre-LT sepsis	0.392 [0.081–1.889]	0.243
Pre-LT dialysis	0.381 [0.079–1,272]	0.105
Pre-LT mechanical ventilation	1.095 [0.227–5,284]	0.910
Pre-LT vasoactive drug use	1.025 [0.256–4,102]	0.972
SBP as a triggering factor	0.517 [0.129–2,073]	0.351
Number of failing organs/systems	1.154 [0.790–1,688]	0.459
CLIF OF	1.042 [0.849–1,278]	0.696
CLIF-C ACLF score	1.013 [0.946–1,085]	0.709

	Hazard ratio [95%CI]	p-value
International normalized ratio	1.007 [0.997–1.018]	0.180
Serum albumin	0.889 [0.560–1.413]	0.619
Total bilirubin	1.015 [0.969–1.064]	0.525

Non-parametric distribution variables by Mann-Whitney test
	Total (n=25)	Alive (n=19; 76%)	Dead (n=6; 24%) Hazard ratio [95%CI]	p-value
	Median	Median	Median	p-value
MELD	32 [IQR_{p 25–75}=27–40]	32 [IQR_{p 25}–₇₅=29–40]	30 [IQR_{p 25}–₇₅=27–37]	0.389
MELD Na	32 [IQR_{p 25}–₇₅=29–40]	33 [IQR_{p 25}–₇₅=29.5–40]	30 [IQR_{p 25}–₇₅=28–37]	0.340
Albumin	2.8 [IQR_{p 25}–₇₅=2.5–3.3]	2.85 [IQR_{p 25}–₇₅=2.55–3.65]	2.8 [IQR_{p 25}–₇₅=2.4–2.8]	0.255
INR	2.5 [IQR_{p 25}–₇₅=1.82–3.04]	2.48 [IQR_{p 25}–₇₅=1.68–2.95]	2.75 [IQR_{p 25}–₇₅=2.31–4.34]	0.308
Total bilirubin	5.6 [IQR_{p 25}–₇₅=2–23.8]	4.5 [IQR_{p 25}–₇₅=1.95–24.3]	14 [IQR_{p 25}–₇₅=1.75–27.15]	0.630
FO number	2 [IQR_{p 25}–₇₅=1–3]	2.5 [IQR_{p 25}–₇₅=1–3]	1 [IQR_{p 25}–₇₅=1–4]	0.571
CLIF OF	12 [IQR_{p 25}–₇₅=9–14]	12 [IQR_{p 25}–₇₅=9–14]	10 [IQR_{p 25}–₇₅=9–13]	0.884
Variables with parametric distribution (mean-CI), t test comparison^* * Fisher’s Exact Test comparison; CI: confidence interval; MELD: model stage liver disease; IQR: interquartile range; MELD Na: model stage Liver Disease sodium; INR: international normalized ratio; CLIF-OF: NO Chronic Liver Failure; CLIF-C: chronic liver failure consortium; ACLF: Acute-on-Chronic Liver Failure; HCV: hepatitis C vírus; ALBI: albumin-bilirubin score.
Male gender	n=11 (44%)	-	-	>99%
Age	52.92 (±10.29)	52.75 (±6.8)	53.2 (±15.04)	0.931
V factor	41.47 (±23.24)	41.59 (±24.75)	41.2 (±21.43)	0.974
CLIF-C ACLF	51 (±10.6)	51 (±9.09)	51.56 (±13.9)	0.930
Sodium	139.36 (±4)	138.94 (±4.25)	140.11(±3.62)	>0.493
Categorical variables, comparison by χ² test
HCV etiology	Total=25 (100%)	n=17 (68%)		0.394
ALBI Grade III	Total=25 (100%)	n=17 (68%)		0.182

	Hazard ratio [95%CI]	p-value
Age	1.045 [0.957–1.140]	0.327
Male gender	0.72 [0.146–3.578]	0.690
MELD	1.011 [0.894–1.144]	0.859
MELD Na	1.012 [0.889–1.152]	0.854
HCV etiology	0.489 [0.099–2.423]	0.381
Total bilirubin	1.013[1.002–1.025]	0.027
INR	1.007 [0.999–1.015]	0.105
Sodium	1.108 [0.895–1.372]	0.346
ALBI	2.547 [0.297–21.817]	0.394
Serum albumin level	1.139 [1.010–1.284]	0.034
Pre-LT sepsis	0.682 [0.124–3.734]	0.659
Pre-LT dialysis	0.349 [0.064–1.906]	0.224
Pre-LT mechanical ventilation	1.940 [0.354–10.616]	0.445
Pre-LT vasoactive drug use	1.986 [0.400–9.849]	0.401
SBP as a triggering factor	0.243 [0.028–2.084]	0.122
Number of failing organs/systems	1.302 [0.822–2.062]	0.261
CLIF OF	1.167 [0.891–1.529]	0.263
CLIF-C ACLF score	1.053 [0.974–1.138]	0.197

	Hazard ratio [95%CI]	p-value
Serum albumin	0.942 [0.535–1.658]	0.836
Total bilirubin (TB)	1.019 [0.964–1.077]	0.504

	All patients (n=25, 100%)	Alive (n=19; 76%)	Dead (n=6; 24%) HR [95%CI]	p-value
	All patients (n=25, 100%)	Median	Median	p-value
MELD	32 [IQR_{p 25–75}=27–40]	32 [IQR_{p 25}–₇₅=27.6–38.5]	31 [IQR_{p 25}–₇₅=27–40]	0.923
MELD Na	32 [IQR_{p 25}–₇₅=29–40]	32 (29–38.5)	31 [IQR_{p 25}–₇₅=29–40]	0.923
Albumin	2.8 [IQR_{p 25}–₇₅=2.45–3.5]	2.8 [IQR_{p 25}–₇₅=2.55–3.6]	2.7 [IQR_{p 25}–₇₅=2.4–2.8]	0.406
INR	2.5 [IQR_{p 25}–₇₅=1.82–3.035]	2.46 [IQR_{p 25}–₇₅=1.82–2.95]	2.8 [IQR_{p 25}–₇₅=2.31–4.34]	0.340
Sodium	139.36 [IQR_{p 25}–₇₅=136–143]	139 [IQR_{p 25}–₇₅=136–142]	141 [IQR_{p 25}–₇₅=138–143]	0.264
Total bilirubin	5.6 [IQR_{p 25}–₇₅=2–23.8]	5.6 [IQR_{p 25}–₇₅=2.1–22.8]	8.9 [IQR_{p 25}–₇₅=1.4–36.6]	0.703
OF number	2 [IQR_{p 25}–₇₅=1–3]	2 [IQR_{p 25}–₇₅=1–3]	2.5 [IQR_{p 25}–₇₅=1–5.5]	0.440
CLIF OF	12 5 [IQR_{p 25}–₇₅=9–14]	10 [IQR_{p 25}–₇₅=9–14]	12.5 [IQR_{p 25}–₇₅=9–16.5]	0.396
Variables with parametric distribution, comparison by t-test
	All patients (n=25, 100%)	Mean	Mean
Male gender	-	11 (44%)	8	0.734
Age	52.9 (±10.29)	51.68 (±9.75)	51.83 (±11.91)	0.295
V factor	185.7(±51.14)	25.9 (±13.8)	44.21 (±23.76)	0.281
CLIF-C ACLF	51.2 (±10.6)	49.79 (±9.25)	55.67 (±13.16)	0.245
Categorical variables, comparison by the χ² test
	Total=25 (100%)	Yes (%)	No (%)
HCV Etilogy	Total=25 (100)	n=17 (68)	n=8 (32)	0.344
ALBI Grade III	Total=25 (100)	n=17 (68)	n=8 (32)	0.624
Pre-LT sepsis	Total=25 (100)	n=10 (40)	n=15 (60)	0.702
Dialysis	Total=25 (100)	n=14 (56)	n=16 (64)	0.199
Pre-LT MV	Total=25 (100)	n=6 (24)	n= 19 (76)	0.606
Vasoactive drug	Total=25 (100)	n=9 (36)	n=16 (64)	0.630
SBP	Total=25 (100)	n=11 (44)	n=14 (56)	0.122

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[1] Correspondence: Marcio Fernandes Chedid. E-mail: marciochedid@hotmail.com

Renal failure (%)	19 (76)
Liver failure (%)	10 (40)
Circulatory failure (%)	11 (44)
Blood coagulation failure (%)	11 (44)
Brain failure (%)	8 (32)
Respiratory failure (%)	2 (8)

Pre-LT hospitalization days, mean±SD	22 (±2.9)
Post-LT hospitalization days, median [IQR_{p 25-75}]	33 [IQR_{p 25–75}=21–45.5]
Post-LT survival 90 days	80%
Post-LT survival 01 year	76%
Post-LT survival 03 years	59.5%
Post-LT survival 05 years	54.1%
Post-LT survival 05 years	54.1%