Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review

Table 5 Studies included for use of plasmapheresis in acute liver failure and acute-on-chronic liver failure in adults

Ref	Type of study/No. of patients recruited	Comparative arm	Plasma exchange regime	Etiology	Results
Xia et al[40]	n = 882; 460 NBAL 422 control; Of which 49 ALF, 46 SALF and 787 ACLF	NBAL (all had PE) vs SMT	All of the patients were treated with PE, and most were treated with one or more additional methods, including 13/26 (50.00%) ALF patients, 16/27 (59.26%) SALF patients, and 228/407 (56.02%) ACLF patients.	For ACLF: 91.24% chronic hepatitis B, 3.69% alcohol abuse, 1.01% autoimmune, 1.01% cholestasis, 3.05% other causes	Clinical outcomes were improved after NBAL treatment. The 30-d survival rates of subacute liver failure (SALF) patients were 63% among those who received NBALs and 21% among those who did not receive NBALs (P < 0.01)
			The choice of therapy was based on each patient’s condition: PE in combination with PP for HE was administered in 12.24% (6/49) of ALF patients, 10.77% (7/65) of SALF patients, and 7.41% (80/1079) of ACLF patients. In patients with HRS, we administered PE with CHDF in 32.65% (16/49) of ALF patients, 23.08% (15/65) sessions of SALF patients and 28.17% (304/1079) sessions of ACLF patients	For ALF: 42% drug toxicity, 16% HBV, 10% surgical trauma, 30% unexplained	The 30-day survival rate of acute-on-chronic liver failure (ACLF) patients who received NBALs was 47%, significantly higher than that of the non-NBAL patients (P < 0.05)
			Pts underwent 1-4 times of NBAL	For SALF: 54% drug toxicity, 30% unexplained, 4% Hepatitis E, 11% HBV	Reported to be effective in biochemical improvement
Cheng et al[12]	Retrospective, cohort study single tertiary centre; n = 55; 10 ALF, 45 ACLF	PE, no comparative arm	PE volume: About 3000 mL, and the exchange rate of plasma was 20-30 mL/min. Heparin was used as anticoagulant during PE	In ALF group: 50% HBV, 20% drug, others include ischemic hepatopathy, traumatic liver injury, HLH	20% (1/5) of the HBV related ALF survived, 1/2 of drug related ALF survived, and 1/1 of the traumatic liver injury related ALF survived.
					Significant improvements see in levels of serum total bilirubin, AST ALT INR PT. No significant changes in ammonia
Nakae et al[21]	Retrospective case series; n = 21; 10 FH; 11 ALF	PDF, no comparative arm	PE volume: 1200mL of normal FFP and 50mL of 25% albumin solution was infused intravenously over 8 h	FH	90 d survival:
				70% Hep B	20% in FH patients
				10% AIH	54.5% in ALF patients
				20% Drug	Overall survival 38.1%
			The PDF session lasted 8h, and the blood flow rate was 100 mL/min. Filtered replacement fluid for was infused at a dialysate flow rate of 600 mL/h and a replacement flow rate of 450 mL/h
					Lower MELD correlated to increased survival
				ALF
					No patients survived beyond 90 d with MELD > 40
					Biochemically: Bilirubin, IL-18 statistially different when compared before and after PDF
				3/11 Unknown
				1/11 GVHD
				4/11 ETOH
				1/11 HBV
			Fluid removal was performed by reducing the replacement flow rate to 450 mL/h at most	1/11 EBV
				1/11 Drug
				5/11 was labelled as AOCLF
Pu et al[34]	Case series (excluding patients who abandoned treatment; n = 33); 8 ALF; 3 SALF; 14 ACLF	CHDF followed by sequential PE, No comparative arm	Patients underwent continuous hemofiltration on a daily basis during the daytime followed by sequential treatment with plasma exchange 1800-2400 mL or hemodialysis every 2-3 d	29 patients with hepatitis B virus infection, 1 with Hepatitis E virus infection, and 3 patients with unknown etiology; 18 were male and 15 female; age ranged from 23 to 65	Restoration of consciousness in 6 of 8 cases (75%) in acute liver failure (ALF) group, 3 of 3 cases (100%) in subacute liver failure (SALF) group, and 9 of 14 cases (64.29%) in acute/subacute on chronic liver failure (A/SCLF) group
					Of all cases, 11 patients restored consciousness after 7 d in a coma. The rate of long-term survival (those who abandoned the treatment were excluded) was 3/7 (42.86%) for ALF group, 2/2 (100%) for SALF group, and 1/11 (9.09%) for A/SCLF group
					No mention of biochemical changes
Schaefer et al[50]	Retrospective cohort study; n = 10; 8 had combined PE, HD + MARS	PE + HD + MARS vs MARS	PE volume: 1.5 plasma volume was exchanged per session within 2–3 h	Wilson’s disease in 2 patients, congenital liver fibrosis, progressive intrahepatic cholestasis, severe combined immunodeficiency, disseminated herpes simplex virus 2 infection, multi-organ failure due to mycoplasma-induced myocarditis, autoimmune hepatitis, fungal sepsis and cetirizine intoxication	MARS and PE/HD treatments were well tolerated by all patients. No bleeding episode occurred. 1 patient with multi-organ failure due to mycoplasma-induced myocarditis, 1 with cetirizine intoxication completely recovered. 3 patients were successfully transplanted, five children died with multi-organ failure and sepsis, including the three children treated with Mini-MARS
			PE was immediately followed by a HD session in six children, using the same extracorporeal circuit with a polysulfone high-flux filter (Fresenius)
					Standard MARS treatment only slightly decreased serum bilirubin (16.3 ± 6.5-13.8 ± 5.9 mg/dL) and ammonia (113 ± 62-99 ± 68 μmol/L) and international normalized ratio (INR) tended to increase (1.5 ± 0.3 and 2 ± 1.1)
	2 had MARS only
					Mini-MARS did not reduce serum bilirubin, ammonia slightly decreased and INR increased
				Age 0.1-18 yr
					PE/HD reduced serum bilirubin (23 ± 8.4-14.7 ± 7 mg/dL), ammonia (120 ± 60–70 ± 40 μmol/L) and INR (2.4 ± 0.8-1.4 ± 0.1, all P < 0.05). Intraindividual comparison showed a slight increase in bilirubin by 2 ± 22% with MARS and a reduction by 37 ± 11% with PE/HD (P < 0.001 vs MARS) and a decrease in ammonia of 18% ± 27% and 39% ± 23% (P < 0.05). INR increased during MARS by 26 ± 41% and decreased with PE/HD by 37 ± 20% (P < 0.01)
Singer et al[51]	Retroespective case series	No comparative arm, TPE in all patients	Plasma volume removed per exchange was 121 ± 47 mL/kg (2.2 ± 0.6 plasma volume) of FFP	57% FHF, 18% BA, 20% IEM, 5% other of note 43% had CLD	Coagulation profiles after TPE significantly improved compared with mean pre-exchange values
					Spontaneous recovery was observed in three patients; the remaining either underwent transplantation (32/49) or were not considered transplant candidates because of irreversible neurologic insults (11/49) or sepsis (3/49)
				Age 10 d to 18.4 yr

PE: Plasma exchange; SMT: Standard medical treatment; ALF: Acute liver failure; HLH: Hemophagocytic lymphohistiocytosis; FFP: Fresh frozen plasma; INR: International normalised ratio; ALT: Alanine aminotransferase; CVVHDF: Continuous venous-venous hemodiafiltration; CHDF: Continuous hemodiafiltration; HBV: Hepatitis B virus; HSV: Herpes simplex virus; LDH: Lactate dehydrogenase; DILI: Drug induced liver injury; AFLP: Acute fatty liver of pregnancy; DILI: Drug induced liver injury; TPE: Therapeutic plasma exchange; BA: Biliary atresia; IEM: Inborn errors of metabolism.