Copyright
©The Author(s) 2020.
World J Gastroenterol. Jan 14, 2020; 26(2): 219-245
Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.219
Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.219
Variable | Description |
Population | Humans diagnosed with liver failure (ALF/ACLF) |
Intervention | Plasma exchange with or without other alternative liver support systems; no restrictions on dose, duration and type of plasma exchange |
Comparator | Randomized controlled trials/Cohort studies: Standard medical treatment |
Case series/case reports: Nil | |
Outcome | All-cause mortality, changes in liver biochemistry, and survival in non-transplanted patients |
Study design | Randomized Controlled Trials, Cohort studies, Case series, Case reports |
Research question | Does plasmapheresis have an effect on all-cause mortality, changes in liver biochemistry, and survival in non-transplanted patients with ALF/ACLF, compared to standard medical treatment? |
Ref. | Type of study/No. of patients recruited | Study group(s) | Plasma exchange regime | Etiology of liver failure | Results/outcome(s) of interest |
Larsen et al[3] | Open randomized control trial; | PE + SMT vs SMT | Plasma exchange volume: Volume of plasma exchange was 15% of ideal body weight (representing 8-12 L per day per procedure); patient plasma was removed at a rate of 1-2 L per hour with replacement with fresh frozen plasma in equivalent volume | Predominantly paracetamol (59%), followed by unknown etiology, toxic hepatitis, viral hepatitis, acute Budd Chiari syndrome | HVP increases transplant free survival after 3 mo, and maximal effect of HVP was achieved in patients who did not undergo emergency transplantation |
n = 182 (Plasma exchange + SMT 92, SMT 90) | |||||
Overall hospital survival was 58.7% for patients treated with high volume plasma exchange vs 47.8% for control group HR: 0.56 (95%CI: 0.36-0.86), P < 0.01 | |||||
However, HVP prior to transplantation did not improve survival compared with patients who received SMT alone P = 0.75 | |||||
HVP procedure was undertaken on three consecutive days but with no fixed time interval between each treatment | |||||
Bilirubin, INR, ALT and ammonia concentration decreased significantly during the first 7 d compared to SMT | |||||
Mean number of HVP = 2.4 ± 0.8 | |||||
Plasma exchange with donor plasma | |||||
Nakae et al[10] | Prospective cohort study; n = 13 | PE vs PE + CHDF | Plasma exchange volume: 3.6 to 4.0 L of plasma was exchanged for the same volume of normal FFP, interval between sessions was 48h or more for both treatment methods | 7 post surgery, 4 fulminant hepatitis, 4 sepsis | Total bilirubin levels were significantly lower after treatment in both arms: Both P < 0.01 in both groups |
No outcomes available on mortality | |||||
Of note, decreased increase in citrate in patients with PE CHDF compared to PE alone | |||||
Plasma exchange with FFP | |||||
Hung et al[5] | Retrospective cohort study; n = 62 (Control 32, PE 30) | PE vs control | Average plasma exchange volume: 2916 mL (range, 1875-3750 mL), plasma exchange occurred over 2 h | 46.7% HBV, 33.3% Drug induced, 6.7% unknown, 33.3% cirrhosis. | At the end of the first week (week 1), the level of total bilirubin and grading of hepatic encephalopathy in the PE group were significantly lower than those in the control group. At the end of the second week (week 2), there were no differences in the level of total bilirubin and grading of hepatic encephalopathy between the two groups of patients |
Difference in survival rate was not significant 66.7% in PE group vs 59.4% in control group | |||||
No significant differences in etiology of liver failure between treatment and control groups | |||||
Average of 6 rounds of exchange per patient (range, 2-15 rounds) | |||||
Difference in survival days were significant, with 17.63 ± 1.86 in PE group vs 8.69 ± 0.86 in control group. P = 0.01 | |||||
Plasma exchange with FFP | |||||
Li et al[4] | Retrospective cohort study; n = 61 | PE + HP + CVVHDF, PE + CVVHDF and HP + CVVHDF | Plasma exchange volume: 2000-3000 mL of fresh per session. Flow rate was 80-120 mL/min, the plasma separation rate was 25-30 mL/min, the replacement time was 2.0-3.0 h | 3/61 acute viral hepatitis, 17/61 chronic toxic acute liver failure. 41 cases of non-viral induced liver injury: 5 after cardiac surgery, 7 with drug poisoning, 13 cases after pregnancy childbirth, 1 case mushroom poisoning, 10 cases with severe infection, 5 others | Treatment of the 61 patients using the artificial liver support system yielded a survival rate of 62.3% (38/61), and a viral survival rate of 35.0% (7/20); with the non-viral survival rate being 75.6% (31/41) Biochemically PE + HP + CVVHDF and PE + CVVHDF groups saw improvement in total bilirubin, ALT, PT, Albumin and HP+CVVHDF saw improvement in total and ALT (P < 0.05) |
In the PE + HP + CVVHDF group: After completion of a single plasma exchange, the HP was carried out. After HP, the CVVHDF is carried out | |||||
Total of 171 exchanges were done | |||||
Nakamura et al[11] | Retrospective case series n = 49; Fulminant hepatitis 15; Severe acute hepatitis 14; Healthy controls 20 | No comparative arm | Plasma exchange volume: Approximately 2000–4000 mL of fresh-frozen plasma was substituted during each exchange | No mention | 10/15 fulminant hepatitis and all severe acute hepatitis survived |
Significant decreases in circulating TNF-a, IL-6, and TGF-ß levels in patients with fulminant hepatitis after a single plasma exchange | |||||
Plasma exchange with FFP | |||||
Akdogan et al[9] | Retrospective case series; n = 39 (fulminant hepatic failure) | PE, No comparative arm | Plasma exchange volume: Total plasma volume approximately 1 | Predominantly undetermined (41%), paracetamol (28.5%), acute hepatitis B, autoimmune liver disease, vascular tumor, acute hepatitis A (in presence of cirrhosis) | Improved biochemically (coagulopathy hyperbilirubinemia, AST, Ammonia, Factor V levels): P < 0.05 |
Plasma exchange continued on a daily basis till clinical response (subjective by ICU team) or patient expired, or transplanted | 31% underwent liver transplant, 92% of which survived at 1 year | ||||
Overall survival 54% (21/39 patients), 37% (10/27) of non-transplanted patients survived | |||||
No need for calcium replacement or magnesium replacement | |||||
Plasma exchange with low volume citrate plasma | |||||
Kondrup et al[6] | Case series; n = 11 | PE, No comparative arm | Plasma exchange volume: 20% body weight plasma exchange intended on three consecutive days, obtained a mean 2.6 exchanges and mean volume 16% body weight | 6 acetaminophen, 2 non-A/B hepatitis, Halothane, disulfurum toxicity and hepatitis B | 5/11 survivors were all acetaminophen toxicity induced ALF |
All had improved bilirubin after treatment | |||||
All 4 Grade IV encephalopathy patients all did not survive | |||||
Plasma exchange with donor plasma. | Those that survived had Grade III encephalopathy or lesser | ||||
Those that did not survive had a longer duration of coma before initiation of PE (3.5 vs 1.8 d) | |||||
Freeman et al[13] | Case series | PE, No comparative arm | Plasma exchange volume: 3 L of plasma exchange was performed daily until conscious level improved or patient died Plasma exchange fluid: Equal volume of compatible fresh frozen plasma and plasma protein fraction (PPF) usually in the proportion of 2 units FFP:1 PPF | 4 acetaminophen, 2 nonA/B hepatitis, 1 hepatitis A, 1 mixed drug overdose, 1 ETOH in 2 | 7/9 showed improvement in coma grades, 5 achieved normal mental state, 5 were able to discharge from hospital. Of which 3 were paracetamol induced liver failure, 1 was monoamine oxidase/ tricyclic acid induced, 1 was alcohol. Survival 55% |
n = 9 | |||||
Improved biochemistry, bilirubin, coagulation (P < 0.01) 1 died of retroperitoneal bleeding | |||||
Buckner et al[7] | Case series | PE, No comparative arm | Plasma exchange volume: Initial 10 L/day plasma exchange with FFP or fresh/outdated plasma | 1 Acute viral hepatitis (pediatric), 2 halothane, 1 hepatitis B viral hepatitis | 1 died (pediatric) |
1 patient took 37 d to awake from coma | |||||
n = 4 (1 pediatric) | |||||
3/4 of patients survived | |||||
Liu et al[31] | Case series | PE, No comparative arm | Plasma exchange volume: Each treatment lasted for 4-6 h, and the total volume exchanged was approximately 7000 mL (1.5-2x TPV) | DILI | The two patients with DILI ALF were treated with PE without need for transplant |
n = 2 | |||||
Biochemically improved after PE (AST ALT Bilirubin) | |||||
Plasma exchange fluid: Maximally, 4700 mL of FFP was exchanged in each session, and the rest comprised plasma substitute consisting of 25% human albumin, pentastarch, 0.9% saline, and Ringer's solution. In each session, the plasma substitute was exchanged initially, and FFP was exchanged at the end | |||||
Duration of PE was based on clinical improvement, both patients had intermittent PE, total 3 sessions | |||||
Bilgir et al[15] | Case report | PE, No comparative arm | Plasma exchange volume: Each session consists of 15 units of FFP, total 4 sessions | L-asparaginase induced ALF | Patient recovered from ALF: However, no biopsy done |
Plasma exchange fluid: FFP | |||||
Aydemir et al[14] | Case report | PE, No comparative arm | Plasma exchange volume: 2500 mL plasma volume removed during each PE session | PTU induced ALF | Patient recovered from ALF: however, no biopsy done |
Plasma exchange fluid: Fresh frozen plasma | |||||
Riveiro-Barciela et al[28] | Letter to editor, case report (Ipilimumab) | PE, No comparative arm | Plasma exchange volume: 1500 mL of 5% albumin plus 4 units of plasma as replacement fluid, carried out every other day for total 5 treatments | Immunotherapy induced ALF | Patient improved. Liver tests within normal values within one month |
Plasma exchange fluid: FFP and 5% albumin | |||||
Damsgaard et al[8] | Case report (ALF in WD) | PE, No comparative arm | Plasma exchange volume: 8-9 L of plasma, total 12 HVP | Fulminant Wilson’s disease ALF | Even though WD ALF score was 16, patient survived without need for OLT |
Plasma exchange fluid: Fresh frozen plasma as replacement fluid 1:1 | |||||
Göpel et al[33] | Case report (Letter to editor) | PE, No comparative arm | Plasma exchange treatment was performed for three consecutive days | Peg-asparaginase induced ALF | Patient improved. Continuous stabilization of fibrinogen and antithrombin 3, an increase of cholinesterase, and a decrease of bilirubin. Clinical signs and symptoms such as jaundice and ascites did also rapidly improve |
No mention of volume or type of exchange fluid | |||||
Lin et al[16] | Case report | PE, no comparative arm | Plasma exchange was performed 2 times per week, and 2000 to 2500 mL frozen plasma was used each time | HLH | Patient’s condition deteriorated, and he died of multi-organ failure during the 6th week of hospitalization. Autopsy was declined |
Chen et al[29] | Case report | PE, No comparative arm | Plasma exchange volume: Estimated two times the plasma volume of the patient was exchanged. At most, 40 units of FFP were exchanged, with the remainder of the infused volume consisting of plasma substitutes. The plasma substitutes consisted of 25% human albumin, pentastarch, normal saline, and Ringer’s solution | Heat stroke | On day 4 after the admission, the patient received high-volume PE (two plasma volumes exchanged). His consciousness was improved a day after PE The patient was discharged on day 16 after admission without sequelae |
Holt et al[17] | Case report | PE, No comparative arm | Plasma exchange on post-partum days 3-5. Volume: Average of 3.2 L (1.6 estimated plasma volumes) of FFP replaced per session, followed by a tapering course of prednisone | AFLP vs HSV hepatitis associated ALF | After 3 d of TPE the patient’s mental status had returned to normal |
Treatment with TPE was followed by biochemical and clinical improvement but during her recovery herpes simplex virus type 2 (HSV‐2) infection was diagnosed serologically and confirmed histologically | |||||
Shen et al[18] | Case report | PE, No comparative arm | Plasma exchange: performed on days 1, 3, and 5, with 3000 mL of plasma exchanged during each session | Occupational Exposure to Tetrachloroethylene | Bilirubin, ammonia, and prothrombin time improved before hospital discharge and patients mental status gradually became normal discharged on day 26 of hospital admission |
Pashaei et al[30] | Case report | PE, No comparative arm | Plasma exchange volume 2.5L | Wilson’s disease | 36 h after initiation of PE, encephalopathy recovered and there was no renal impairment. Copper, LDH total bilirubin decreased after the treatment |
Plasma exchange fluid: FFP |
Ref. | Type of study / No. of patients recruited | Study group(s) | Plasma exchange regime | Etiology; Age | Results |
Pham et al[19] | Case series | PE, No comparative arm | Plasma volume: Targeted 1-1.25 plasma volumes | Wilsons Disease | Post TPE 9 patients underwent liver transplantation and all 10 patients had at least 6 mo survival |
n = 10 | |||||
Age 6-61 yr | |||||
Median days from first to OLT was 1-53 d | |||||
Plasma exchange fluid: 77% of procedures were performed with plasma as sole replacement fluid while 23% used the combination of plasma and 5% albumin | |||||
Median number of TPE: 3.5 | |||||
Chien et al[22] | Retrospective case series | PE, No comparative arm | Plasma exchange volume: Plasma exchange was usually performed daily for the first 3 d, and then shifted to every other day or every 3 d according to the patient's condition | 60% idiopathic, 17% infection, 8% metabolic and immunologic, 4% toxin | 11 (48%) had native liver recovery (NLR), 9 (39.1%) died without liver transplant, and 3 (12.9%) received liver transplantation |
The no liver recovery group showed a lower proportion of idiopathic cases, lower peak ammonia level, higher peak alpha fetoprotein (AFP) level, and they had plasma exchange fewer times than the other groups | |||||
n = 23 | |||||
Age 0.29-9.25 yr | |||||
Plasma exchange volume: 2–4 times the patient’s estimated plasma volume | |||||
Plasma exchange fluid: FFP | |||||
Ide et al[47] | Retrospective case series | PE/CVVHDF, No comparative arm | CVVHDF and PE were applied in all ALF patients | 2/17 viral | All laboratory results relating to liver dysfunction decreased significantly after CVVHDF + PE |
1/17 mitochondrial | |||||
PE using 100 mL/kg of FFP per treatment course was implemented once daily for 6 to 8 h until the recovery of coagulopathy | Overall survival rate 88% with median follow up period of 28 mo | ||||
14/17 indeterminate | |||||
n = 17 | |||||
Age 1-11 mo [Median Weight 8.0 (2.7-10 kg)] | |||||
Verma et al[23] | Case report | PE, No comparative arm | Plasma exchange volume: 1.5-2 h, 1.2 L plasma exchange in each session, in addition to oral D penicillamine and Zinc | Wilson’s disease | Patient improved initially but subsequently deteriorated fter developing renal failure and shock, and died from acute pulmonary hemorrhage. |
Age 5 yr (Weight: 15 kg) | |||||
Morgan et al[25] | Case report | PE, No comparative arm | Plasma exchange volume: 1500 mL TPE, 5 single plasma volume over 11 d in addition to trientine | Wilson’s disease | Patient had worsening bilirubin, coagulopathy despite treatment and underwent OLT 12 d after beginning TPE |
Plasma exchange fluid: Plasma | Age 6 years | ||||
Zhang et al[24] | Case report | PE, No comparative arm | Plasma exchange volume: 1200 mL each time, with blood flow velocity of 45–50 mL/min, plasma separation speed of 650–750 mL/h, and a replacement time of approximately 2 h. Total 9 exchanges | Wilson’s disease | CPFA started after PE. The patient had rapid recovery of consciousness, removal of copper and stabilization of serum bilirubin and hemoglobin. 9 d after last PE patient underwent liver transplant. |
Plasma exchange fluid: FFP | Age 7 yr (Weight 21 kg) | ||||
Yukselmis et al[26] | Case report | PE, No comparative arm | Plasma exchange volume: 1.5 times total blood volume then 1 time for the subsequent courses | Viral (Influenza) | Patient did not require transplantation in light of clinical improvement and PE resulted in complete recovery |
Total 3 sessions PE on top of ostelmavir | Age 4 yr (Weight 16 kg) | ||||
Plasma exchange fluid: FFP | |||||
Ponikvar et al[27] | Case report | PE+HD, No comparative arm | Plasma exchange volume: 3 volumes of plasma (12% of body weight of 16 kg) per procedure were exchanged (1972 ± 85 mL; range, 1800–2150 mL). FFP was used as the replacement solution. An equal volume of plasma was removed and replaced | Unknown Excluded viruses and metabolic cause | Patient did not improve after 1 mo and was referred to a liver transplant center and successfully transplanted. Patient also had hyperbaric oxygen (HBO) during treatment |
Age 3 yr (Weight 16 kg) | |||||
A total of 13 PEs, 13 HD sessions, and 9 HBO treatments over a period of 1mo. The initial 4 PEs were followed by HD sessions while the other 8 PE treatments were given simultaneously with HD. There was no renal failure; HD was instituted to improve ammonia elimination | |||||
Harmanci et al[48] | Case report / Letter to editor | PE, No comparative arm | Plasma exchange volume: 2.5 L per session | Wilson’s Disease | Patients mental status improved and was extubated and weaned from mechanical ventilation on the fifth day of hospitalization. The patient did not require liver transplantation. The patient was treated continously with zinc and D-penicillamine |
Age 17 yr | |||||
Started daily and continued for 7 consecutive days |
Ref. | Type of study/Number of patients recruited | Study group(s) | Characteristics of study population | Plasma exchange regime | Etiology | Results |
Meng et al[39] | Retrospective cohort study, single center; n = 158; PE group: 38; SMT group: 120 | PE vs SMT | PE group: Higher MELD score | Performed twice a week until patients’ condition was stable, additional weekly or biweekly visits were instituted if patients felt deterioration of their condition. Total duration of therapy 2-8 wk | Hepatitis B | 24/38 (63%) death in the PE group and 82% in SMT group died within 4 wks. By week 12, 71% in PE group and 86% in SMT group died |
Baseline characteristics both groups had 26%-28% of patients with hepatic encephalopathy | ||||||
ACLF definition: ACLF was defined as serum bilirubin ≥ 5 mg/dL and an INR 1.5 or prothrombin activity (PTA) 40 %, complicated within 4 wk by ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver diseases | 18% vs 14% transplant free survival in 3 mo comparing PE vs SMT (P < 0.01) | |||||
Plasma exchange volume not mentioned | ||||||
Biochemically, there is decreased bilirubin in PE arm cf SMT (P < 0.01) | ||||||
Mao et al[38] | Retrospective cohort study, single center | PE vs SMT | ACLF definition: Acute decompensation of liver function in patients with chronic preexisting liver diseases. ACLF is defined as a syndrome with severe jaundice (total bilirubin: 171 mmol/L), coagulopathy (prolonged prothrombin time, prothrombin activity 40%), or hepatic encephalopathy (above grade II) | Plasma exchange volume: 3500 mL at 25-30 mL/min. A total of 3000–4500 mL of fresh frozen plasma (40-60 mL/kg) and 20-40 g of human albumin were supplied | Hepatitis B. Drug hepatitis, Wilson disease, alcoholic liver disease, autoimmune hepatitis excluded | 26 survivors and 36 non-survivors were in the PE group, whereas 33 survivors and 98 non-survivors were in the control group after 30 d treatment. Their survival rates were 41.9% and 25.2% for PE and medical therapy, respectively (P < 0.05) |
Baseline characteristics 74%-77% had HE at baseline | ||||||
PE group: 62 | ||||||
SMT group 131 | ||||||
No mention re: Biochemical improvement | ||||||
Flow rate of blood was adjusted to 60–130 mL/min | ||||||
Not randomised | ||||||
PE was carried out 2-3 times per week for the first two weeks, then weekly, then stopped based on clinical results | ||||||
Chen et al[42] | Retrospective cohort study multicentre (10) | PE, no comparative arm | ACLF definition: Guidelines for Diagnosis and Treatment of Liver Failure in China (2006): Early stage is defined as a progressively deepening jaundice (Bilirubin level ≥ 171 μmol/L or a daily increase of ≥ 17.1 μmol/L), PTA > 30% but ≤ 40%, and no HE or other complications. Middle-stage disease represents progression of the symptoms of the early stage, including one of the following symptoms: Grades I/II HE, ascites, or a PTA of > 20% but ≤ 30%. In the end-stage disease, the condition deteriorates further with a PTA of ≤ 20% and includes one of the following symptoms: Hepatic-renal syndrome, severe upper gastrointestinal bleeding, serious infection, and grades III/IV HE | Plasma exchange volume: 2500-3500 mL, and the PE rate was 20-25 mL/min | Hepatitis B | Forty-two of the 52 (80.8%) patients in the early stage, seventy-five of the 99 (75.8%) patients in the middle stage and thirty-seven of the 99 (37.4%) patients in the end stage survived for one month after diagnosis |
n = 250 patients | ||||||
Dexamethasone (5 mg) and heparin (2500 U) were injected routinely before PE | ||||||
Authors concluded that late stage ACLF might benefit from PE as a bridge to definitive treatment-liver transplant | ||||||
PE was repeated every 2-4 d | ||||||
Zhou et al[45] | Retrospective, cohort | PBA + PE vs PE | ACLF was defined as acute liver injury emerging as jaundice and coagulopathy, complicated by ascites and/or encephalopathy within 4 wk in a patient with known or unknown chronic liver disease. The definition of liver failure in ACLF was as follows: Severe jaundice (total serum bilirubin ≥ 5 mg/dL) and coagulopathy (INR ≥ 1.5 or prothrombin activity < 40%) and ascites and/or encephalopathy. | Plasma exchange volume: Approximately 3000 mL of plasma was exchanged per time at a blood flow rate of 20 to 25 mL/min | HBV 56.6%, HBV+HEV 31.9% Others 11.5% | The mean overall survival for the derivation cohort was 441 d (95%CI: 379-504), and the 90- and 270-d survival probabilities were 70.3% and 58.3%, respectively |
Derivation cohort 113 | ||||||
Validation cohort 68 | The mean survival times of patients treated with PBA plus PE and patients treated with PE were 531 days (95%CI: 455-605) and 343 d (95%CI: 254-432), respectively (P = 0.012) | |||||
From the derivation cohort: PE, n = 54; PE+PA, n = 59 | ||||||
Each patient in the derivation cohort received PE 1 to 4 times | ||||||
Predictors of survival: Age, MELD, Complication, type of ALSS No mention re: Baseline characteristics of PE vs PBA | ||||||
Baseline population in this study is 51% cirrhotic | ||||||
Wan et al[44] | Prospective cohort study | PE vs DPMAS | ACLF was defined as serum bilirubin 5 mg/dL and INR > 1.5 or PTA < 40%, complicated within 4 wk by ascites and/or HE in patients with previously diagnosed or undiagnosed chronic liver diseases | Plasma exchange volume: About 3000 mL of plasma exchanged at an exchange rate of 20-30 mL/min at each session. | HBV | During the study, a total of 42 patients died, with 24 in TPE group and 18 in DPMAS group. The median survival times were 12 wk in TPE group and 11 wk in DPMAS group |
n = 60 | ||||||
TPE 33 | PE was performed 2-3 times/week, lasting 2-3 h every session | The 4-wk and 12-wk survival rates in TPE group and DPMAS group were 87.9% and 88.9%, 34.6% and 33.3%, respectively. There was no marked difference in survival between the two groups | ||||
DPMAS 27 | Baseline eAg positive greater in TPE group (18% vs 7.4%) | |||||
Bilirubin removal in TPE more efficient compared to DPMAS | ||||||
Qin et al[37] | Open label randomized controlled parallel group single-center study | PE centered ALSS vs SMT | Definition of ACLF was according to the Chinese guidelines, Bilirubin ≥ 10 mg/dL, PTA ≤ 40% and cirrhosis and multiorgan failure were not taken as mandatory criteria, according to the Chinese guidelines | PE volume: 3500 mL (40–60 mL/kg) FFP, at 25-30 mL/min | HBV | Survival rates after 90 d were 60% (62/104) in ALSS-treated patients and 47% (61/130) in the control group. (P < 0.05). The 5-year cumulative survival rates of the ALSS and control groups were 43% (45/104) and 31% (40/130), respectively (P < 0.05) |
ALSS schedule: 3 routine treatments were performed in the first 10 d after inclusion in the study (once per 3–4 d); extra treatments were offered according to the improvement of the patients. The methods of PE-centered ALSS were chosen based on clinical conditions. For patients with coagulopathy, PE was applied; for patients with encephalopathy, PE plus hemoperfusion or continuous hemodiafiltration was used; for patients complicated with HRS or imbalance of water or electrolytes, PE plus continuous hemodiafiltration was used | ||||||
n = 234 | ||||||
No mention of biochemical improvement | ||||||
Xia et al[40] | Retrospective cohort study | NBAL (all had PE) vs SMT | ACLF definition: | 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%) Subacute ALF 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) |
1 Acute deterioration of pre-existing chronic liver disease | ||||||
n = 882 | ||||||
460 NBAL 422 control | 2 Extreme fatigue with severe digestive symptoms, such as obvious anorexia, abdominal distension or nausea and vomiting | |||||
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) | ||||||
Of which 49 ALF, 46 SALF and 787 ACLF | ||||||
3 Progressively worsening jaundice within a short period (serum total bilirubin ≥ 10 mg/dL or a daily elevation ≥ 1 mg/dL) | ||||||
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 | ||||||
Reported to be effective in biochemical improvement | ||||||
4 Obvious hemorrhagic tendency with PTA ≤ 40% (PT ≥ 18.3 s or INR > 1.50) | ||||||
The absence of any of the above four criteria precluded a diagnosis of ACLF | ||||||
Pts underwent 1-4 times of NBAL each | ||||||
Li et al[49] | Prospective cohort Study | PE vs PE + UCMSCs | ACLF was defined as serum bilirubin ≥ 5 mg/dL and INR ≥ 1.5 or PTA < 40%, complicated within 4 wk by ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver disease | PE volume: About 3000 mL, and the exchange rate of plasma was 20–30 mL/min. Heparin was used as anticoagulant during PE | HBV | The cumulative survival rates at 3 mo in group A and group B were 54.5 % and 29.4 %, respectively (P = 0.015 by log rank test) |
PE: 34 | ||||||
INR was prominently lower in PE + UCMSCs group than in PE group (P < 0.05). At 12 mo, patients in PE+UCMSCs group showed lower levels of AST than patients in PE group (P < 0.05). | ||||||
PE+UCMSCs: 11 | ||||||
n = 45 | ||||||
In PE group: MELD score: 22.5 +/- 1.4, 61.8% cirrhotic | At 24 mo, patients in PE+UCMSCs group had significantly improved levels of albumin, PT and INR than patients in PE group (P < 0.05). However, ALT, Total bilirubin, Direct bilirubin, creatinine, white blood cell, Hemoglobin, Platelet and ascites were comparable at each follow-up | |||||
Xu et al[43] | Retrospective cohort study | PE | Definition of ACLF: Acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 wk by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease | Total volume exchanged 3300 mL | HBV | 1-yr and 5-yr survival rates in the ALSS-LT group and LT group were 79.2% and 83%, 69.7% and 78.6% |
n = 171 | ||||||
Patients with coagulopathy were indicated for PE, when the patient had HE, PE + hemodiafiltration was used. For patient with hepatorenal syndrome or imbalance of water or electrolytes, PE + continuous hemodiafiltration or MARS was used | ||||||
PE before LTx: 115 | ||||||
Emergent LTx: 56 | ||||||
PE group: MELD score 31+/-6 | ||||||
Yao et al[41] | Retrospective cohort study | PE vs DPMAS + PE | Definition of ACLF: Acute hepatic insult manifesting as jaundice and coagulopathy, complicated within 4 wk by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease | PE volume: Fresh frozen plasma was 2200 to 2400 mL per treatment. Duration of single treatment was about 2 h | HBV | The total bilirubin levels immediately after treatment at 24 and 72 h after treatment were markedly decreased in DPMAS + PE group compared to that in PE group (52.3 ± 9.4% vs 42.3 ± 7.2%, P < 0.05; 24.2 ± 10.0% vs 13.5 ± 13.0%, P < 0.05; 24.8 ± 13.1% vs 14.9 ± 14.9%, P < 0.05; respectively). |
n = 131 | ||||||
PE group (n = 77) | Patients underwent 1-4 times of PE / PE + DPMAS | |||||
DPMAS + PE group (n = 54) | Baseline characteristics were similar in both groups | |||||
The 28- d survival rates was 62.3% and 72.2% in PE and DPMAS + PE groups (P = 0.146). | ||||||
28- d survival rates were significantly higher in DPMAS + PE group than that in PE group (57.4% vs 41.7%, P = 0.043) in the intermediate-advanced stage patients | ||||||
Cheng et al[12] | Retrospective, cohort study single tertiary centre | PE, no comparative arm | ACLF definition: acute hepatic insult that manifests as jaundice (serum bilirubin ≥ 5 mg/dL and coagulopathy (INR ≥ 1.5), which is complicated within 4 wk by clinical ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease or cirrhosis | The processed plasma volume was approximately 3000 mL for each session (1-1.5 total plasma volume); the blood flow rate was 100 mL/min; and the PE rate was 25–30 mL/min, with an equivalent volume of replacement fluid using fresh frozen plasma | Hepatitis B (75%) in ACLF group, 6% alcohol, others: HCV, AIH | Biochemical improvements seen after PE: AST/ALT/Bil/INR |
Average 4-5 sessions of PE in ACLF group, 3-5 sessions in ALF | ||||||
n = 55; 10 ALF, 45 ACLF | ||||||
Initial diagnosis to PE is longer in non-survivors in ACLF and ALF though not significant | ||||||
Survival based on etiology of ACLF: 24% HBV, 67% ETOH, 0% HBV + alcohol, 0% HCV 0% HCV + alcohol, 0% AIH | ||||||
79% of patients with ACLF have cirrhosis, 55% have grades III-IV HE | PE occurred daily or every other day till sustained clinical improvement, liver transplantation or no clinical response/death |
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 |
- Citation: Tan EXX, Wang MX, Pang J, Lee GH. Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review. World J Gastroenterol 2020; 26(2): 219-245
- URL: https://www.wjgnet.com/1007-9327/full/v26/i2/219.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i2.219