Table 1 Characteristics of included studies
First author, publication year | Eligibility criteria | Etiology of the underlying disease and baseline characteristics | Intervention(s) and/or comparison | Outcomes |
|---|---|---|---|---|
Banares (2013) | Inclusion: presumptive diagnosis of cirrhosis with an identifiable triggering event; an increase of TBIL > 5 mg/dl and at least one of the following: HRS, HE ≥ grade II, rapidly progressive hyperbilirubinemia (> 50% increase from TBIL levels at admission) > 20 mg/dl at admission Exclusion: progressive jaundice as a consequence of the natural course of cirrhosis; extrahepatic cholestasis; PLT < 50,000/mm3; INR > 2.3; suspected or evident DIC; need for RRT; intrinsic renal disease; uncontrolled infection; active bleeding; HCC > 4 cm in diameter; portal vein thrombosis; severe cardiopulmonary disease; MAP < 60 mmHg despite vasopressor therapy; major surgical procedure within the last 4 weeks; HIV infection | Mostly alcoholic; viral, autoimmune, drug-induced, NASH, etc. Age (years)a: 51.8/50.0 Males (%): 66.7/70.8 MELDa:25.6/24.1 | MARS/SMT | Survival, HE, laboratory parameters, AEs |
Duan (2018) | Inclusion: 15–65 years; clinical diagnosis of ACLF; obvious gastrointestinal and/or systemic toxic symptoms; TBIL > 5 times upper limit of normal or daily increase > 1 mg/dl; prothrombin activity of 10–50%; INR 1.6–4.0, or prothrombin time > 5 s longer than the control but < 20 s, HE absent or grade I–II; no or mild ascites/pleural effusion Exclusion: primary or metastatic liver cancer; uncontrolled severe infection; shock; active bleeding within 3 days; grade III–IV HE; PLT < 40 × 109/l; creatinine > 1.5 mg/ml; severe esophageal varices | Mostly alcoholic and viral; drug-induced, autoimmune, unknown, “acute/subacute” Agea (years): 39.5/39.2 Males (%): 96.9/88.2 MELDa: 28.0/30.8 | ELAD/SMT | Survival, AEs |
Ellis (1999) | Inclusion: acute alcoholic hepatitis, HE ≥ grade II Exclusion: pregnancy; MAP < 50 mmHg despite adequate volume loading and appropriate use of inotropes; respiratory failure; cerebrovascular event within the previous 12 months, a recent upper gastrointestinal hemorrhage; poorly controlled epilepsy; recent myocardial infarction/ischemia | Alcoholic Ageb (years): 46/43 Males (%): 60/80 MELD/CTP: NR | BioLogic-DT/SMT | Survival, HE, physical and laboratory parameters, AEs |
Hassanein (2007) | Inclusion: ≥ 18 years, manifestations of cirrhosis and HE grade III–IV Exclusion: active hemorrhage; hemodynamic instability; acute cardiopulmonary complications (pulmonary edema, massive aspiration pneumonia, heart failure); pregnancy; active RRT; drug intoxication or irreversible brain damage or nonhepatic causes of altered mental status; acute liver failure; HCC; received transplant | Mostly alcoholic or viral; autoimmune, drug induced, unknown Ageb (years): 49/56 Males (%): 61.5/48.4 MELDb: 33/38 | MARS/SMT | HE, AEs, laboratory parameters (survival is additional) |
Heemann (2002) | Inclusion: 18–65 years; cirrhosis (CTP ≥ 7) and a superimposed acute liver injury leading to decompensation and severe hyperbilirubinemia (TBIL ≥ 20 mg/dl) Exclusion: hepatobiliary obstruction; active bleeding or sepsis causing hemodynamic instability; comorbid conditions associated with a poor outcome; coma of nonhepatic origin; extensive surgery 30 days preceding admission; HRS; pregnancy | Mostly alcoholic; viral, drug induced Ageb (years): 48/57 Males (%): 50/63.6 CTPb: 11.5/12 | MARS/SMT | Survival, HE, AEs, laboratory parameters |
Hillebrand (2010) | Inclusion: acute decompensation of cirrhosis; SOFA score ≥ 9; and either a MELD score of ≥ 32, or MELD ≥ 24 and at least one of HE grade III–IV or type I HRS Exclusion: NR | Etiology, age, sex NR MELDa: 34.3/40.8 | ELAD/SMT | Survival, AEs |
Huang (2012) | Inclusion: chronic severe hepatitis B with HE ≥ grade II Exclusion: late stage disease; previous irreversible respiratory failure; severe brain edema with hernia; severe systemic circulation disorder accompanied by DIC; serious active bleeding | HBV Ageb (years): 43/42 Males (%): 78.3/75 MELD/CTP: NR | MARS ± PE | Survival, HE, AEs, laboratory parameters, cost of treatment |
Kramer (2001) | Inclusion: documented cirrhosis and encephalopathy grade II or III had not improved with conventional treatment Exclusion: renal failure; hypotension (MAP < 55 mmHg); respiratory or multiorgan failure; fever of > 38.5 °C; bleeding requiring transfusion of > 2 units within the preceding 24 h; insulin-dependent diabetes mellitus; administration of sedatives within the preceding 2 days | Alcoholic, viral, autoimmune, unknown Ageb (years): 55/56 Malesc (%): 65% CTPb: 14/14.5 | BioLogic-DT/SMT | HE, laboratory and physical parameters, AEs (survival is additional) |
Kribben (2012) | Inclusion: 18–70 years; severe deterioration of chronic liver disease; CTP ≥ 10 (over 72 h); TBIL ≥ 5 mg/dl (over 72 h) Exclusion: pregnancy/lactation; HIV infection, intracranial bleeding; cerebrovascular disease; ARDS; circulatory shock with vasopressor therapy; persistent bleeding needing perfusion; chronic renal failure stage V; acute necrotizing pancreatitis; HCC, malignancy; INR > 3.0 or PLT < 30,000/l; extrahepatic cholestasis; liver resections or major hepatobiliary surgery in the previous 6 months except laparoscopic cholecystectomy; LT within 2 years, ALSS therapy within 7 days; participation in another clinical trial or this study priorly | Mostly alcoholic and viral; others not specified Agea (years): 50/51 Males (%): 62/65 MELDb: 28/27 | Prometheus/SMT | Survival, laboratory parameters; AEs |
Mitzner (2000) | Inclusion: 18–60 years; HRS (serum creatinine > 1.5 mg/dl, oliguria < 500 ml/d, urine sodium < 20 mmol/l, central venous pressure > 8 cmH2O); need of hemodialysis/filtration treatment; chronic liver failure (3 of 4 criteria): ultrasonic signs of chronic damage or impaired synthesis function (hypoalbuminemia, 30 g/l, prolonged prothrombin time (quick value < 70%), AT III < 70%, serum cholinesterase < 40 umol/s/l) or hyperbilirubinemia (> 15 mg/dl) or grade III–IV HE Exclusion: fulminant hepatic failure; sepsis unresponsive to antibiotics; severe acute hemorrhages; malignancies; obstructive/chronic renal failure; pregnancy; severe cardiopulmonary disease | Mostly alcoholic; HBV, primary and secondary biliary cirrhosis Agea (years): 49.6/43.8 Males (%): 37.5/40 CTPa: 12.5/12.2 | MARS/SMT | Survival |
Pyrsopoulos (2019) | Inclusion: SAH, age 18–50 years, total bilirubin ≥ 16 mg/dl, Maddrey score ≥ 32, not eligible for transplant Exclusion: PLT < 40,000/mm3; INR > 2.5; serum creatinine ≥ 1.3 mg/dl; MELD score ≥ 30; AST > 500 IU/l; infection unresponsive to antibiotics; reduction in TBIL ≥ 20% in the previous 72 h; hemodynamic instability; active bleeding; major hemorrhage; liver size reduction due to cirrhosis; occlusive portal vein thrombosis; bile duct obstruction; life expectancy of less than 3 months due to concomitant diseases; subject on hemodialysis; Wilson’s disease; NAFLD; Budd-Chiari syndrome; active viral hepatitis; pregnancy; received liver transplant | Alcoholic hepatitis Agea (years): 39.1/39.5 Males (%): 60.3/60.3 MELDa: 24.8/25.6 | ELAD/SMT | Survival, AEs |
Qin (2014) | Inclusion: 18–70 years; presumptive diagnosis of chronic hepatitis B infection, HBV-associated cirrhosis, or hepatitis B surface antigen (HBsAg) carrier; rapidly progressive hyperbilirubinemia with TBIL > 10 mg/dl, within 28 days from symptom onset; INR > 1.5 or plasma prothrombin activity < 40% Exclusion: acute HBV infection; hepatitis E, A, D, or HIV superinfection; alcohol- or drug-induced liver injury; severe gastrointestinal bleeding; HCC; pregnancy | HBV Agea (years): 44.1/48.7 Males (%): 82.7/72.3 MELDa: 28.6/29.5 | PE/SMT | Survival, AEs |
Sen (2004) | Inclusion: 18–75 years old; alcoholic liver disease; acute deterioration in liver function over 2–4 weeks leading to severe progressive clinical deterioration despite supportive care (over 48 h); jaundice (TBIL > 100 mol/l) and either HE Grade II or HRS; cirrhosis Exclusion: prior enrollment in another study; known hepatic/extrahepatic malignancy; uncontrolled infection or upper gastrointestinal bleeding over the previous 48 h; pregnancy; prior treatment with terlipressin for HRS; coexisting HIV infection; severe cardiorespiratory disease | Alcoholic Ageb (years): 45/44 Males (%): 78/67 MELDb: 16.5/19.4 | MARS/SMT | Survival, HE, laboratory and physical parameters |
Teperman (2012) | Inclusion: acute alcoholic hepatitis or acute decompensation of cirrhosis, MELD 18–35 Exclusion: NR | Alcoholic and not specified (baseline only given for PP subjects) | ELAD/SMT | Survival, time to progression, AEs |
Thompson (2018) | Inclusion: ≥ 18 years, history of heavy alcohol abuse, maximum of 6 weeks between the last consumption, rapid onset of jaundice (TBIL ≥ 8 mg/dl), and coagulopathy (Maddrey's DF ≥ 32), stratum A: liver biopsy confirmed SAH/ 2 of the following: AST > ALT, leukocytosis, ascites stratum B: SAH + underlying chronic liver disease confirmed by biopsy, laboratory findings, and/or medical history Exclusion: end-stage cirrhosis; portal vein thrombosis; MELD > 35, PLT < 40,000/mm3; severe concomitant disease; uncontrolled bleeding; infection unresponsive to antibiotics; hemodynamic instability; chronic dialysis | Alcoholic hepatitis (superimposed or primary) Agea (years): 46.5/44.8 Males%: 57.3/60.7 MELDa: 27.6/27.1 | ELAD/SMT | Survival, laboratory parameters, AEs |
Yu (2008) | Inclusion: acute-on-chronic hepatitis B liver failure (HBV-DNA ≥ 10,000 copies/mL); defined as severe jaundice (TBIL > 171 mmol/l), coagulopathy, and/or HE > grade II; previous lamivudine treatment; MELD > 30 Exclusion: obstructive and hemolytic jaundice; prolonged prothrombin time due to hematologic diseases; drug-induced hepatitis; Wilson's disease; alcoholic liver disease; autoimmune hepatitis; hepatitis C or D or HIV infection | HBV Agea (years): 45.2/46.4 Males (%): 80/78.6 MELDa,d: 41.4 | PE/SMT | Survival, laboratory parameters |
He (2000)* | Inclusion: severe viral hepatitis according to the criteria of the 1995 national symposium Exclusion: NR | Mostly viral; alcoholic Age, sex, MELD/CTP: NR | PE, PP, DHP/SMT | Survival, laboratory parameters, HE, AEs |
Hu (2005)* | Inclusion: chronic severe hepatitis complicated with multiorgan failure Exclusion: NR | NR | MARS/SMT | Survival, HE, laboratory parameters |
Krisper (2005)* | Inclusion: ACLF Exclusion: NR | Mostly alcoholic; HCV Agec (years): 57 Malesc (%): 67% MELDb: 35.4 | MARS and Prometheus, crossover | Laboratory parameters, AEs |
Laleman (2006)* | Inclusion: 18–75 years; histologically proven alcoholic cirrhosis with superposed alcoholic hepatitis; portal hypertension with associated hyperdynamic circulation and ACLF (persistent deterioration in liver function despite treatment of the precipitating event and elevated bilirubin > 12 mg%) Exclusion: extrahepatic cholestasis; coma of nonhepatic origin; active gastrointestinal bleeding in the past 5 days; comorbidities associated with poor outcome (acute necrotizing pancreatitis, neoplasia, severe cardiopulmonary disease, oxygen-dependent or steroid-dependent COPD); ongoing infection; HRS type I | Alcoholic Agea (years): 54.5/43.2/55.8 Males (%): 83.3/66.7/50 MELDa: 22.7/29.7/24.3 | MARS/Prometheus /SMT | Laboratory parameters, AEs |
Meijers (2012)* | Inclusion: ≥ 18 years, compensated chronic liver disease; developed intrahepatic cholestasis (TBIL > 5 mg/dl); at least one of the following complications within 4–8 weeks after a potential identifiable acute superposed hepatic insult: (a) a progressive hyperbilirubinemia ≥ 50% increase of TBIL > 20 mg/dl, (b) HE grade ≥ II, (c) de novo development of ascites, and/or (d) HRS Exclusion: extrahepatic cholestasis; severe hypocalcemia (Ca2+ < 0.9 mmol·l−1); acidosis (pH < 7.25) | Mostly alcoholic; HCV, NASH, and others Agec (years): 54.6 Males (%): NR MELDa,c: 32.1 | MARS ± citrate, crossover | Laboratory parameters, AEs |
Wilkinson (1998)* | Inclusion: decompensated chronic liver disease and grade III–IV encephalopathy Exclusion: NR | Alcoholic, HCV, HBV, autoimmune, unknown Agea (years): 58.3/42.7 Males (%): 60/100 MELD/CTP: NR | BioLogic-DT/SMT | Physiologic and neurologic improvement, AEs |
You (2011)* | Inclusion: ACLF defined by the Chinese Medical Association’s definition (2006) Exclusion: NR | Viral (?) Agea (years): 42.7/43.5 Males (%): 100/83 MELDa: 23/24.1 | HBALSS/PE | Survival, AEs, laboratory parameters |