FATORES PROGNÓSTICOS DE TRANSPLANTE HEPÁTICO EM “ACUTE-ON-CHRONIC LIVER FAILURE”

CRONST, Jane; PREDIGER, Lucas; PINTO, Marcelo Abreu; FERRAZ, Julia; MATTOS, Angelo Zamban de; ALVARES-DA-SILVA, Mario Reis; KRUEL, Cleber Rosito Pinto; CHEDID, Marcio Fernandes

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ABCD. Arquivos Brasileiros de Cirurgia Digestiva (São Paulo)

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Sumário

Original Article • ABCD, arq. bras. cir. dig. 36 • 2023 • https://doi.org/10.1590/0102-672020230061e1779 copiar

FATORES PROGNÓSTICOS DE TRANSPLANTE HEPÁTICO EM “ACUTE-ON-CHRONIC LIVER FAILURE”

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

RACIONAL:

O transplante hepático (TH) é o único tratamento a proporcionar sobrevida a longo prazo para pacientes com “acute-on-chronic liver failure” (ACLF). Vários estudos identificaram fatores prognósticos para pacientes em ACLF que não realizam TH, porém há poucos dados na literatura sobre fatores prognósticos nessa população transplantada.

OBJETIVOS:

Avaliar desfechos de pacientes ACLF submetidos a TH, e seus preditores de mortalidade.

MÉTODOS:

Foram avaliados pacientes em ACLF submetidos a TH entre janeiro de 2005 e abril de 2021. Variáveis como valores CLIF-C ACLF e pontuação no ACLF foram comparadas com os desfechos.

RESULTADOS:

A sobrevida de ACLF pós TH de pacientes (n=25) em 90 dias, 1, 3, 5 e 7 anos, foi de 80, 76, 59,5, 54,1 e 54,1% versus 86,3, 79,4, 72,6, 66,5 e 61,2% para pacientes submetidos a TH por outras indicações (n=344), (p=0,525). Não houve diferença estatística para mortalidade em 01 ano e 90 dias entre pacientes com os três graus de ACLF (ACLF-1 vs. ACLF-2 vs. ACLF-3), bem como quando comparados a pacientes não ACLF. O escore “chronic liver failure consortium” (CLIF-C) ACLF não se correlacionou com desfechos de óbito. Nenhuma das outras variáveis estudadas mostrou-se preditora independente de mortalidade em 90 dias, após um ano ou global.

CONCLUSÕES:

TH conferiu sobrevida em longo prazo à maioria dos pacientes transplantados, semelhante aos pacientes submetidos à TH por outras indicações. Nenhuma das variáveis estudadas mostrou-se fator prognóstico associado a desfechos de sobrevida pós-TH para pacientes com ACLF. Estudos adicionais são necessários para estabelecer fatores prognósticos pós-TH em pacientes com ACLF.

DESCRITORES:
Transplante de Fígado; Cirrose Hepática; Falência Hepática Aguda; Gastroenterologia; Sobrevida

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%