Jong Won Choi; Ki Tae Yoon; Jun Yong Park; Ja Kyung Kim; Sang Hoon Ahn; Yong Han Paik; Kwan Sik Lee; Kwang-Hyub Han; Chae Yoon Chon; Do Young Kim

doi:10.4166/kjg.2009.54.1.28

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Choi, Yoon, Park, Kim, Ahn, Paik, Lee, Han, Chon, and Kim: Usefulness and Safety of Extracorporeal Liver Support Therapy Using MARSⓇ for Patients with Liver Failure: A Preliminary Report

Original Article

Korean J Gastroenterol 2009;54(1):28-35.

Published online: 21 February 2009

DOI: https://doi.org/10.4166/kjg.2009.54.1.28

Usefulness and Safety of Extracorporeal Liver Support Therapy Using MARS^Ⓡ for Patients with Liver Failure: A Preliminary Report

Jong Won Choi, M.D., Ki Tae Yoon, M.D., Jun Yong Park, M.D., Ja Kyung Kim, M.D., Sang Hoon Ahn, M.D., Yong Han Paik, M.D., Kwan Sik Lee, M.D., Kwang-Hyub Han, M.D., Chae Yoon Chon, M.D., Do Young Kim, M.D.

Department of Internal Medicine, Liver Cirrhosis Clinical Research Center, Yonsei University College of Medicine, Seoul, Korea

Correspondence to: Do Young Kim, M.D. Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 250, Seongsan-ro, Seodae-mun-gu, Seoul 120-752, Korea Tel: +82-2-2228-1992, Fax: +82-2-393-6884 E-mail: dyk1025@yuhs.ac

Received 18 October 2008 Accepted 23 December 2008

Abstract

Background/Aims

The molecular adsorbent recirculating system (MARS^Ⓡ) is a form of artificial extracorporeal liver support and can be used for a bridge to spontaneous recovery of hepatic function or liver transplantation in patients with liver failure. This study evaluated the usefulness of MARS^Ⓡ in patients with liver failure.

Methods

Between January 2004 and July 2007, 30 patients (21 males and 7 females; age 48.9±12.9 years) with acute or acute-on-chronic liver failure were managed using MARS^Ⓡ. We assessed laboratory data, the grade of hepatic encephalopathy, Child-Turcotte-Pugh class, and Model for End-Stage Liver Disease (MELD) score.

Results

The number of patients with acute liver failure and acute-on-chronic liver failure was 16 and 14, respectively. The mean cycle of MARS^Ⓡ in patients with liver failure was 2.2 sessions. After MARS^Ⓡ had been performed, serum total bilirubin, alanine aminotransferase (ALT), BUN, creatinine, ammonia level, daily urine output, and MELD score were improved (p＜0.05). In contrast, MARS^Ⓡ failed to improve Child-Turcotte-Pugh score and the grade of hepatic encephalopathy. Liver transplantation was performed in 8 patients. Among them, 5 (62.5%) patients survived and 3 (37.5%) patients died. Twenty two patients underwent MARS^Ⓡ without liver transplantation and 4 (18.2%) of them survived.

Conclusions

In patients with liver failure, MARS^Ⓡ improved the laboratory data and hepatic and renal function associated clinical characteristics. However, MARS^Ⓡ without liver transplantation did not improve survival. MARS^Ⓡ may be useful as a bridge therapy to liver transplantation in patients with liver failure.

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Keywords: Liver failure, Molecular adsorbent recirculating system (MARS^Ⓡ), Liver transplantation

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Fig. 1.

MARS^Ⓡ in patients with acute liver failure. ALF, acute liver failure; LT, liver transplantation.

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Fig. 2.

MARS^Ⓡ in patients with acute-on-chronic liver failure. AoCLF, acute-on-chronic liver failure; LT, liver transplantation.

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Table 1.

Etiology of the Patients with Liver Failure

Acute liver failure		Acute-on-chronic liver failure
Etiology	n=16 (%)	Etiology	n=14 (%)
Drug-induced liver injury	8 (50.0)	LC (chronic hepatitis B)	9 (64.3)
Hepatitis B flare-up	3 (18.6)	Alcoholic liver disease	4 (28.6)
Acute hepatitis A	1 (6.3)	Unknown	1 (7.1)
Ischemic hepatitis	1 (6.3)
Wilson's disease	1 (6.3)
Unknown	2 (12.5)

Hepatitis B flare-up, acute exacerbation of chronic hepatitis B; Acute hepatitis A, acute infection of hepatitis A virus; Ischemic hepatitis, liver injury by reducing oxygen delivery to liver; LC, liver cirrhosis

Table 2.

General Characteristics of the Patients with Liver Failure

Characteristics	n=30 (%)
Age (yr)	48.9＋12.9^∗
Male	21 (70.0)
CTP score	11.9＋1.9^∗
MELD score	31.7＋8.5^∗
History of varix bleeding	7 (23.3)
Oliguria	4 (13.3)
Furosemide administration (IV)	20 (66.7)
Terlipressin treatment (IV)	3 (10.0)
Serum creatinine ＞2.0 mg/dL	6 (20.0)
Plasma ammonia ＞150μ g/dL	16 (53.3)
Prothrombin time (INR)＞2.0	19 (63.3)
Hepatic encephalopathy grade III, IV	11 (36.7)
Refractory ascites	16 (53.3)

CTP score, Child-Turcotte-Pugh class; MELD, model for end-stage liver disease; IV, intravenous injection; INR, international normalization ratio of prothrombin time.∗ Mean± SD.

Table 3.

Laboratory Data and Clinical Characteristics before and after MARS^Ⓡ in 30 Patients with Liver Failure (Total 67 Cycles)

	Pre-MARS^Ⓡ	Post-MARS^Ⓡ	p-value
Total bilirubin (mg/dL)	34.4±13.9	28.3±11.9 ＜	＜0.001
AST (IU/L)	378.2±1,230.4	432.6±1,821.8	8 0.381
ALT (IU/L)	294.3±835.7	250.1±700.6	0.002
BUN (mg/dL)	28.3±23.4	20.4±14.6 ＜	＜0.001
Creatinine (mg/dL)	1.56±1.45	1.37±0.96	0.044
Albumin (g/dL)	3.40±0.55	3.38±0.62	0.503
Ammonia (μ g/dL)	193.2±101.4	166.2±82.5	0.021
Hemoglobin (g/dL)	10.12±1.95	9.51±1.72	0.001
Platelets (×1,000/mm³)	110.9±77.1	90.5±62.1 ＜	＜0.001
Prothrombin time (INR)	2.945±1.679	2.991±1.750	0.183
CTP score	11.9±1.8	11.8±1.8	0.458
MELD score	31.1±10.0	30.0±9.6	0.043
Grade of HE	2.0±1.4	1.9±1.4	0.157

INR, international normalization ratio of prothrombin time; CTP score, Child-Turcotte-Pugh score; MELD, model for end-stage liver disease; HE, hepatic encephalopathy. p-value calculated by Wilcoxon signed rank test.

Table 4.

Laboratory Data and Clinical Characteristics before and after MARS^Ⓡ

	Acute liver failure (n=16) (Total 42 cycles)			Acute-on-chronic liver failure (n=14)(Total 25 cycles)
	Pre-MARS^Ⓡ	Post-MARS^Ⓡ	p-value	Pre-MARS^Ⓡ	Post-MARS^Ⓡ	p-value
Total bilirubin (mg/dL)	34.7±16.3	27.2±13.8	＜0.001	34.0±8.5	30.2±7.4	＜0.001
AST (IU/L)	516.9±1,523.9	567.7±2,276.6	0.118	145.1±325.0	205.5±433.0	0.628
ALT (IU/L)	436.3±1,029.2	362.5±864.0	＜0.001	55.7±129.6	61.2±124.2	0.730
BUN (mg/dL)	23.9±24.4	17.3±15.5	＜0.001	35.8±19.9	25.6±11.4	＜0.001
Creatinine (mg/dL)	1.56±1.58	1.40±1.00	0.380	1.56±1.25	1.32±0.90	0.022
Albumin (g/dL)	3.47±0.53	3.40±0.64	0.892	3.27±0.56	3.35±0.59	0.183
Ammonia (μ g/dL)	194.6±113.8	159.5±84.4	0.011	190.8±80.0	176.5±80.5	0.550
Hemoglobin (g/dL)	10.43±1.93	9.65±1.78	0.003	9.61±1.91	9.27±1.63	0.082
Platelets (×1,000/mm³)	135.5±87.4	110.7±70.6	＜0.001	70.4±25.0	58.2±20.3	0.003
Prothrombin time (INR)	3.098±1.9385	2.968±1.903	0.682	2.969±1.108	3.027±1.511	0.005
CTP score	11.3±1.9	11.3±1.8	0.817	12.7±1.3	12.6±1.4	0.257
MELD score	30.8±11.4	29.6±10.2	0.092	31.6±7.2	30.8±8.6	0.226
Grade of HE	2.1±1.4	2.1±1.5	0.564	1.8±1.2	1.7±1.3	0.180

INR, international normalization ratio of prothrombin time; CTP score, Child-Turcotte-Pugh class; MELD, model for end-stage liver disease; HE, hepatic encephalopathy. p-value calculated by Wilcoxon signed rank test.

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