Growing Evidence for Survival Benefit with Plasma Exchange to Treat Liver Failure
2023; Elsevier BV; Volume: 13; Issue: 6 Linguagem: Inglês
10.1016/j.jceh.2023.06.002
ISSN2213-3453
AutoresAshish Goel, Uday Zachariah, Dolly Daniel, C. E. Eapen,
Tópico(s)Alcohol Consumption and Health Effects
ResumoPlasma exchange (PLEX) to treat liver failure patients is gaining increasing momentum in recent years. Most reports have used PLEX to treat patients with acute liver failure (ALF) or acute on chronic liver failure (ACLF). Etiology of liver disease has an important bearing on the prognosis of the illness in these patients. The accruing data suggest survival benefit with PLEX compared with standard medical treatment to treat ALF and ACLF patients, in randomised controlled trials done world-over. The American College of Apheresis now recommends high-volume PLEX as first-line treatment for ALF patients. Most matched cohort studies done from India which recruited patients with a specific etiology of ALF or ACLF report survival benefit with PLEX compared to standard medical treatment. The survival benefit with PLEX appears more pronounced in ALF patients rather than in ACLF patients. Systematic analysis of the efficacy of PLEX to treat ALF and ACLF patients is needed. There is also a need to identify dynamic predictive scores to assess which patients with ALF or ACLF will respond to PLEX. Plasma exchange (PLEX) to treat liver failure patients is gaining increasing momentum in recent years. Most reports have used PLEX to treat patients with acute liver failure (ALF) or acute on chronic liver failure (ACLF). Etiology of liver disease has an important bearing on the prognosis of the illness in these patients. The accruing data suggest survival benefit with PLEX compared with standard medical treatment to treat ALF and ACLF patients, in randomised controlled trials done world-over. The American College of Apheresis now recommends high-volume PLEX as first-line treatment for ALF patients. Most matched cohort studies done from India which recruited patients with a specific etiology of ALF or ACLF report survival benefit with PLEX compared to standard medical treatment. The survival benefit with PLEX appears more pronounced in ALF patients rather than in ACLF patients. Systematic analysis of the efficacy of PLEX to treat ALF and ACLF patients is needed. There is also a need to identify dynamic predictive scores to assess which patients with ALF or ACLF will respond to PLEX. Plasma exchange (PLEX) to treat liver failure involves two steps—removal of plasma from a patient with liver failure and replacing this with equal volume of fluid; in view of the coagulopathy seen in liver failure patients, the preferred fluid for replacement is fresh frozen plasma. In contrast to hemodialysis, hemadsorption filter or albumin dialysis which remove specific substances (for example: albumin dialysis removes albumin-bound substances), plasma exchange involves the removal of plasma (with all the substances contained in it) and replaces this with healthy donor fresh frozen plasma. Therapeutic plasma exchange is referred to by many abbreviations in literature like PLEX, TPE or PEX. While PLEX has been used to treat neurological disorders (like Guillain Barre syndrome), hematological disorders (like thrombotic thrombocytopenic purpura) and renal disorders (like hemolytic uremic syndrome) for decades, the use of PLEX to treat liver failure is relatively recent. Liver failure can be categorised as five phenotypes: hyperacute liver failure, acute liver failure (ALF), subacute liver failure, chronic liver failure (cirrhosis) and acute on chronic liver failure (ACLF).1Acharya S.K. Acute liver failure: Indian perspective.Clin Liver Dis. 2021 Jul 22; 18: 143-149Crossref PubMed Scopus (6) Google Scholar ALF can include hyperacute liver failure and subacute liver failure as per some definitions. As ALF and ACLF patients have high short-term mortality, urgent liver transplantation is needed as a life-saving treatment. PLEX has been recently reported to be beneficial to treat ALF and ACLF patients. Viral hepatitis and idiosyncratic drug reaction are major causes of ALF in different parts of India. In southern, eastern and central India, rodenticide ingestion to commit suicide is an important cause of ALF. The true burden of ALF patients in any state of India or in the whole country is not known at present. Of ∼1000 liver transplants done each year in India, 5–7.5% (ie. 50–75 patients) are performed for ALF patients.1Acharya S.K. Acute liver failure: Indian perspective.Clin Liver Dis. 2021 Jul 22; 18: 143-149Crossref PubMed Scopus (6) Google Scholar It was estimated that rodenticide ingestion (phosphorus poisoning) causing ALF in one state in India (Tamil Nadu) alone would have resulted in the death of 554 patients in the year 2019.2Govindarajan R. Ramamoorthy G. Shanmugam R.M. et al.Rodenticide ingestion is an important cause of acute hepatotoxicity in Tamil Nadu, southern India.Indian J Gastroenterol. 2021 Aug; 40: 373-379Crossref PubMed Scopus (8) Google Scholar There is an urgent need to provide liver transplantation as well as non-transplant treatments to save the lives of ALF and ACLF patients. An average adult has about 5 L of blood (about 2.5 L is plasma). High, standard and low volume PLEX refer to 10 L (4 times the plasma volume), 2.5–5 L (1–2 times the plasma volume) or 1.2 L of plasma (0.5 times the plasma volume) exchanged per session of PLEX. Different doses of PLEX have been used to treat liver failure patients with high3Larsen F.S. Schmidt L.E. Bernsmeier C. et al.High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial.J Hepatol. 2016 Jan; 64: 69-78Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar,4Pawaria A. Sood V. Lal B.B. Khanna R. Bajpai M. Alam S. Ninety days transplant free survival with high volume plasma exchange in Wilson disease presenting as acute liver failure.J Clin Apher. 2021 Feb; 36: 109-117Crossref PubMed Scopus (12) Google Scholar, standard5Maiwall R. Bajpai M. Singh A. et al.Standard-volume plasma exchange improves outcomes in patients with acute liver failure: a randomized controlled trial.Clin Gastroenterol Hepatol. 2022 Apr; 20: e831-e854Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar or low volume PLEX,6Thomas L. Chandran J. Goel A. et al.Improving transplant-free survival with low-volume plasma exchange to treat children with rodenticide induced hepatotoxicity.J Clin Exp Hepatol. 2023 Mar-Apr; 13: 252-258Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar to treat ALF and standard7Qin G. Shao J.G. Wang B. et al.Artificial liver support system improves short- and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure: a single-center experience.Medicine (Baltim). 2014 Dec; 93: e338https://doi.org/10.1097/MD.0000000000000338Crossref PubMed Scopus (66) Google Scholar, 8Yu J.W. Sun L.J. Zhao Y.H. Li S.C. Prediction value of model for end-stage liver disease scoring system on prognosis in patients with acute-on-chronic hepatitis B liver failure after plasma exchange and lamivudine treatment.J Gastroenterol Hepatol. 2008 Aug; 23: 1242-1249Crossref PubMed Scopus (56) Google Scholar, 9Maiwall R. Bajpai M. Choudhury A.K. et al.AARC working Party. Therapeutic plasma-exchange improves systemic inflammation and survival in acute-on-chronic liver failure: a propensity-score matched study from AARC.Liver Int. 2021 May; 41: 1083-1096Crossref PubMed Scopus (21) Google Scholar, 10Swaroop S. Arora U. Biswas S. et al.Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: a propensity score-matched analysis.J Clin Apher. 2022 Nov 21; (Epub ahead of print. PMID: 36408827)https://doi.org/10.1002/jca.22033Crossref PubMed Scopus (1) Google Scholar, 11Ramakrishnan S. Hans R. Duseja A. Sharma R.R. Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.J Clin Apher. 2022 Dec; 37: 553-562Crossref PubMed Scopus (2) Google Scholar or low volume PLEX12Kumar S.E. Goel A. Zachariah U. Nair S.C. et al.Low volume plasma exchange and low dose steroid improve survival in patients with alcohol-related acute on chronic liver failure and severe alcoholic hepatitis - preliminary experience.J Clin Exp Hepatol. 2022 Mar-Apr; 12: 372-378Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar to treat ACLF. Higher volume of PLEX, adds relatively little to the clearance (and efficiency), but increases the risk of transfusion-related complications like volume overload.13Kaplan A.A. Moderator's view: high-volume plasma exchange: pro, con and consensus.Nephrol Dial Transplant. 2017 Sep 1; 32: 1464-1467Crossref PubMed Scopus (13) Google Scholar The volume of plasma exchanged in the landmark trial by Larsen et al.3Larsen F.S. Schmidt L.E. Bernsmeier C. et al.High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial.J Hepatol. 2016 Jan; 64: 69-78Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar was decided arbitrarily.14Larsen F.S. Low volume plasma exchange to treat children with acute liver failure.J Clin Exp. Hepatol. 2023 Mar-Apr; 13: 191-192Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar It was hypothesised that the failing liver was not able to remove toxic substances which then accumulated in plasma and contributed to the development of multi-organ failure in ALF patients. High-volume PLEX aimed to replace this toxic plasma with healthy donor fresh frozen plasma. Preliminary data suggest that low-volume PLEX may also be beneficial to treat ALF patients.6Thomas L. Chandran J. Goel A. et al.Improving transplant-free survival with low-volume plasma exchange to treat children with rodenticide induced hepatotoxicity.J Clin Exp Hepatol. 2023 Mar-Apr; 13: 252-258Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Apart from strain on blood bank resources (large volumes of fresh frozen plasma needed), risk of transfusion associated acute lung complications, risk of blood borne virus infection, and so on make the use of low-volume PLEX attractive compared to high-volume PLEX.14Larsen F.S. Low volume plasma exchange to treat children with acute liver failure.J Clin Exp. Hepatol. 2023 Mar-Apr; 13: 191-192Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Centrifugal or membrane techniques can be used for PLEX. In centrifugal PLEX, the cells in the blood are separated from plasma by molecular-density-based separation during centrifugation (this is the same process used to fractionate blood components in blood banks). In contrast, membrane PLEX uses a filter to separate plasma from cells in the blood (ie. separation based on molecular size). Centrifugal PLEX provides higher plasma removal efficacy than membrane PLEX.15Hafer C. Golla P. Gericke M. et al.Membrane versus centrifuge-based therapeutic plasma exchange: a randomized prospective crossover study.Int Urol Nephrol. 2016 Jan; 48: 133-138Crossref PubMed Scopus (44) Google Scholar Some differences in the two PLEX techniques of relevance in treating liver failure patients are worth noting. Higher rates of blood flow needed for membrane PLEX may result in hemodynamic fluxes which may further adversely affect the perfusion in the compromised hepatic microcirculation. In contrast, the low flow rates with centrifugal PLEX make hemodynamic alterations less likely in liver failure patients. Also, in membrane PLEX, when blood is filtered across a membrane, the already activated blood cells may be further activated, worsening the inflammatory milieu in the liver. Most studies report the use of centrifugal PLEX to treat liver failure. Preliminary data suggest centrifugal PLEX is superior to membrane PLEX to treat patients with very severe alcoholic hepatitis/alcohol-related ACLF.16Kumar S.E. Singh K.A. Daniel D. et al.Therapeutic plasma exchange by centrifugal technique has survival benefit at 1 year over membranous technique in patients with severe alcoholic hepatitis.J Clin Exp Hepatol. 2022; 12 (S 14)https://doi.org/10.1016/j.jceh.2022.07.052Abstract Full Text Full Text PDF Google Scholar Randomised controlled trials (RCTs) provide the highest quality of evidence on whether a therapeutic intervention improves survival. However, the evident benefits as well as challenges in carrying out these trials in patients with ALF have meant that liver transplantation is accepted as standard treatment, without RCTs.17Wendon J. Cordoba J. Dhawan A. et al.EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure.J Hepatol. 2017 May; 66: 1047-1081Abstract Full Text Full Text PDF PubMed Scopus (531) Google Scholar Another approach is to compare survival in matched cohorts of ALF or ACLF patients treated with PLEX or with standard medical treatment (SMT). Propensity score matching can be done to better match patients in the two treatment arms. Etiology has a significant bearing on prognosis in ALF patients.17Wendon J. Cordoba J. Dhawan A. et al.EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure.J Hepatol. 2017 May; 66: 1047-1081Abstract Full Text Full Text PDF PubMed Scopus (531) Google Scholar The King's college hospital criteria identified ALF due to idiosyncratic drug reaction or non-A non-B viral hepatitis had worse prognosis in non-paracetamol overdose induced ALF.18O'Grady J.G. Alexander G.J. Hayllar K.M. Williams R. Early indicators of prognosis in fulminant hepatic failure.Gastroenterology. 1989 Aug; 97: 439-445Abstract Full Text PDF PubMed Google Scholar In a multi-centre study, survival rates with native liver were highest in ALF due to paracetamol overdose (57%) or hepatitis A (40%) and least due to Wilson's disease (0% survival).19Schiodt F.V. Atillasoy E. Shakil A.O. et al.Etiology and outcome for 295 patients with acute liver failure in the United States.Liver Transplant Surg. 1999 Jan; 5: 29-34Crossref PubMed Scopus (351) Google Scholar The nature of the acute liver insult influences the severity and outcome of ACLF. Alcohol or cryptogenic ACLF patients had more severe liver disease, higher incidence of organ failures and higher risk of death than hepatitis B- or E-related ACLF.20Shalimar Kedia S. Mahapatra S.J. Nayak B. Gunjan D. Thakur B. et al.Severity and outcome of acute-on-chronic liver failure is dependent on the etiology of acute hepatic insults: analysis of 368 patients.J Clin Gastroenterol. 2017 Sep; 51: 734-741Crossref PubMed Scopus (36) Google Scholar In alcohol-related ACLF, metabolic risk factors may impact disease severity and short-term mortality.21Duseja A. De A. Taneja S. et al.APASL ACLF Working Party, APASL ACLF Research Consortium (AARC)Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.Liver Int. 2021 Jan; 41: 150-157Crossref PubMed Scopus (13) Google Scholar Herbal drug-induced liver injury adversely influences survival in alcoholic hepatitis.22Philips C.A. Rajesh S. George T. Ahamed R. Kumbar S. Augustine P. Outcomes and toxicology of herbal drugs in alcoholic hepatitis - a single center experience from India.J Clin Transl Hepatol. 2019 Dec 28; 7: 329-340Crossref PubMed Scopus (5) Google Scholar There are now a plethora of reports on use of PLEX to treat patients with liver failure. A recent meta-analysis studied RCTs on use of PLEX to treat ALF and ACLF. In this meta-analysis, 4 RCTs (ALF: 2 studies, ACLF: 2 studies) with 736 patients (356 patients had PLEX, 380 patients had SMT) were included. Of ALF patients, 75% was caused by acute viral hepatitis; 57% had advanced encephalopathy; 81% were on mechanical ventilation and 50% on inotropes. This meta-analysis reported better survival at 3 months in patients treated with PLEX than SMT [odds ratio 2.41; 95% confidence interval (CI, 1.28,4.56), P = 0.007].23Mohamed M.M.G. Osman A. El-Halawany H. Plasma exchange for patients with acute or acute on chronic liver failure; meta-analysis of randomized controlled trials.Clin Res Hepatol Gastroenterol. 2022 Dec; 46102014https://doi.org/10.1016/j.clinre.2022.102014Crossref PubMed Scopus (1) Google Scholar A review of reports comparing PLEX with SMT to treat patients with ALF or ACLF is given in Table 1 (we included RCTs from world-over and matched cohort studies from India). The compiled data in RCTs suggest survival benefit with PLEX to treat ALF or ACLF. Most matched cohort studies of patients of a single etiology (like ALF caused by Wilson's disease4Pawaria A. Sood V. Lal B.B. Khanna R. Bajpai M. Alam S. Ninety days transplant free survival with high volume plasma exchange in Wilson disease presenting as acute liver failure.J Clin Apher. 2021 Feb; 36: 109-117Crossref PubMed Scopus (12) Google Scholar or by rodenticide ingestion [phosphorus poison]6Thomas L. Chandran J. Goel A. et al.Improving transplant-free survival with low-volume plasma exchange to treat children with rodenticide induced hepatotoxicity.J Clin Exp Hepatol. 2023 Mar-Apr; 13: 252-258Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar or ACLF caused by alcohol12Kumar S.E. Goel A. Zachariah U. Nair S.C. et al.Low volume plasma exchange and low dose steroid improve survival in patients with alcohol-related acute on chronic liver failure and severe alcoholic hepatitis - preliminary experience.J Clin Exp Hepatol. 2022 Mar-Apr; 12: 372-378Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar) also show survival benefit with PLEX. The survival benefit with PLEX seems to be more pronounced in ALF than in ACLF patients.Table 1Randomised Controlled Trials (RCTs) Conducted Worldover and Matched Cohort Studies (Cohort) From India on Efficacy of Plasma Exchange (PLEX) to Treat Patients With Acute Liver Failure (ALF) or Acute on Chronic Liver Failure (ACLF). Survival Shown is at 21 days or at End of Hospital Stay in ALF Patients and at 3 months in ACLF Patients.Survival with PLEX vs. standard medical treatment to treat liver failureSignificantly worseTrend to worsenEquivocalTrend to improveSignificantly betterALFRCT–13Larsen F.S. Schmidt L.E. Bernsmeier C. et al.High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial.J Hepatol. 2016 Jan; 64: 69-78Abstract Full Text Full Text PDF PubMed Scopus (401) Google ScholarRCT–25Maiwall R. Bajpai M. Singh A. et al.Standard-volume plasma exchange improves outcomes in patients with acute liver failure: a randomized controlled trial.Clin Gastroenterol Hepatol. 2022 Apr; 20: e831-e854Abstract Full Text Full Text PDF PubMed Scopus (29) Google ScholarCohort–14Pawaria A. Sood V. Lal B.B. Khanna R. Bajpai M. Alam S. Ninety days transplant free survival with high volume plasma exchange in Wilson disease presenting as acute liver failure.J Clin Apher. 2021 Feb; 36: 109-117Crossref PubMed Scopus (12) Google Scholar Cohort–26Thomas L. Chandran J. Goel A. et al.Improving transplant-free survival with low-volume plasma exchange to treat children with rodenticide induced hepatotoxicity.J Clin Exp Hepatol. 2023 Mar-Apr; 13: 252-258Abstract Full Text Full Text PDF PubMed Scopus (8) Google ScholarACLFCohort–310Swaroop S. Arora U. Biswas S. et al.Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: a propensity score-matched analysis.J Clin Apher. 2022 Nov 21; (Epub ahead of print. PMID: 36408827)https://doi.org/10.1002/jca.22033Crossref PubMed Scopus (1) Google ScholarCohort–411Ramakrishnan S. Hans R. Duseja A. Sharma R.R. Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.J Clin Apher. 2022 Dec; 37: 553-562Crossref PubMed Scopus (2) Google ScholarCohort–29Maiwall R. Bajpai M. Choudhury A.K. et al.AARC working Party. Therapeutic plasma-exchange improves systemic inflammation and survival in acute-on-chronic liver failure: a propensity-score matched study from AARC.Liver Int. 2021 May; 41: 1083-1096Crossref PubMed Scopus (21) Google ScholarRCT–17Qin G. Shao J.G. Wang B. et al.Artificial liver support system improves short- and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure: a single-center experience.Medicine (Baltim). 2014 Dec; 93: e338https://doi.org/10.1097/MD.0000000000000338Crossref PubMed Scopus (66) Google ScholarRCT–28Yu J.W. Sun L.J. Zhao Y.H. Li S.C. Prediction value of model for end-stage liver disease scoring system on prognosis in patients with acute-on-chronic hepatitis B liver failure after plasma exchange and lamivudine treatment.J Gastroenterol Hepatol. 2008 Aug; 23: 1242-1249Crossref PubMed Scopus (56) Google ScholarCohort–112Kumar S.E. Goel A. Zachariah U. Nair S.C. et al.Low volume plasma exchange and low dose steroid improve survival in patients with alcohol-related acute on chronic liver failure and severe alcoholic hepatitis - preliminary experience.J Clin Exp Hepatol. 2022 Mar-Apr; 12: 372-378Abstract Full Text Full Text PDF PubMed Scopus (10) Google ScholarPLEX, Plasma exchange; ALF, Acute liver failure; ACLF, acute on chronic liver failure. Open table in a new tab Table 2Randomised Controlled Trials Comparing Survival with Plasma Exchange (PLEX) or Standard Medical Treatment (SMT) to Treat Patients with Acute Liver Failure or Acute on Chronic Liver Failure.EtiologyDose of PLEXSurvival without liver transplantationIncrease in survival with PLEX than with SMTReferenceAcute liver failureMost common: paracetamol overdoseHigh volumeIn - hospital survival10.9%Larsen et al.3Larsen F.S. Schmidt L.E. Bernsmeier C. et al.High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial.J Hepatol. 2016 Jan; 64: 69-78Abstract Full Text Full Text PDF PubMed Scopus (401) Google ScholarPLEX (n = 92)SMT (n = 90)58.7%47.8% (P = 0.008)Most common: viral hepatitisStandard volume21 day survival30%Maiwall et al.5Maiwall R. Bajpai M. Singh A. et al.Standard-volume plasma exchange improves outcomes in patients with acute liver failure: a randomized controlled trial.Clin Gastroenterol Hepatol. 2022 Apr; 20: e831-e854Abstract Full Text Full Text PDF PubMed Scopus (29) Google ScholarPLEX (n = 20)SMT (n = 20)75%45% (P = 0.04)Acute on chronic liver failure (survival at 3 months)Hepatitis BStandard volumePLEX (n = 104)SMT (n = 130)13%Qin et al.7Qin G. Shao J.G. Wang B. et al.Artificial liver support system improves short- and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure: a single-center experience.Medicine (Baltim). 2014 Dec; 93: e338https://doi.org/10.1097/MD.0000000000000338Crossref PubMed Scopus (66) Google Scholar60%47% (P < 0.05)Hepatitis BStandard volumePLEX (n = 140)SMT (n = 140)Yu et al.8Yu J.W. Sun L.J. Zhao Y.H. Li S.C. Prediction value of model for end-stage liver disease scoring system on prognosis in patients with acute-on-chronic hepatitis B liver failure after plasma exchange and lamivudine treatment.J Gastroenterol Hepatol. 2008 Aug; 23: 1242-1249Crossref PubMed Scopus (56) Google ScholarMELD 30 - 4051%14% (P < 0.01)37%MELD >408%2% (P > 0.05)6%PLEX, Plasma exchange; SMT, standard medical treatment. Open table in a new tab Table 3Matched Cohort Studies From India Comparing Survival with Plasma Exchange (PLEX) to Standard Medical Treatment (SMT) to Treat Patients with Acute Liver Failure or Acute on Chronic Liver Failure.EtiologyDose of PLEXSurvival without liver transplantationReferenceAcute liver failureWilson's diseaseHigh volume90 day survivalPawaria et al.4Pawaria A. Sood V. Lal B.B. Khanna R. Bajpai M. Alam S. Ninety days transplant free survival with high volume plasma exchange in Wilson disease presenting as acute liver failure.J Clin Apher. 2021 Feb; 36: 109-117Crossref PubMed Scopus (12) Google Scholar ILBS DelhiPLEX (n = 19)SMT (n = 18)47%17% (P = 0.049)Rodenticide (phosphorus) poison in childrenLow volume30 day survivalaSurvival in patients who met Kochi listing criteria for liver transplantation in rodenticidal hepatotoxicity patients was compared with historical cohort.24Thomas et al.6Thomas L. Chandran J. Goel A. et al.Improving transplant-free survival with low-volume plasma exchange to treat children with rodenticide induced hepatotoxicity.J Clin Exp Hepatol. 2023 Mar-Apr; 13: 252-258Abstract Full Text Full Text PDF PubMed Scopus (8) Google ScholarCMC VellorePLEX (n = 10)SMT (n = 8)60%0%Acute on chronic liver failure (survival at 3 months)AlcoholLow volumePLEX (n = 21)SMT (n = 29)Kumar et al.12Kumar S.E. Goel A. Zachariah U. Nair S.C. et al.Low volume plasma exchange and low dose steroid improve survival in patients with alcohol-related acute on chronic liver failure and severe alcoholic hepatitis - preliminary experience.J Clin Exp Hepatol. 2022 Mar-Apr; 12: 372-378Abstract Full Text Full Text PDF PubMed Scopus (10) Google ScholarCMC Vellore38%14%Most common: alcoholStandard volumePLEX (n = 38)SMT (n = 38)Swaroop et al.10Swaroop S. Arora U. Biswas S. et al.Therapeutic plasma-exchange improves short-term, but not long-term, outcomes in patients with acute-on-chronic liver failure: a propensity score-matched analysis.J Clin Apher. 2022 Nov 21; (Epub ahead of print. PMID: 36408827)https://doi.org/10.1002/jca.22033Crossref PubMed Scopus (1) Google ScholarAIIMS Delhi63%47% (P = 0.17)AlcoholbOnly APASL ACLF grade 2 patients recruited in this study.Standard volumePLEX (n = 14)SMT (n = 14)Ramakrishnan et al.11Ramakrishnan S. Hans R. Duseja A. Sharma R.R. Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.J Clin Apher. 2022 Dec; 37: 553-562Crossref PubMed Scopus (2) Google ScholarPGI Chandigarh64%50% (P = 0.22)PLEX, Plasma exchange; SMT, standard medical treatment.a Survival in patients who met Kochi listing criteria for liver transplantation in rodenticidal hepatotoxicity patients was compared with historical cohort.24Saraf V. Pande S. Gopalakrishnan U. et al.Acute liver failure due to zinc phosphide containing rodenticide poisoning: clinical features and prognostic indicators of need for liver transplantation.Indian J Gastroenterol. 2015 Jul; 34: 325-329Crossref PubMed Scopus (35) Google Scholarb Only APASL ACLF grade 2 patients recruited in this study. Open table in a new tab PLEX, Plasma exchange; ALF, Acute liver failure; ACLF, acute on chronic liver failure. PLEX, Plasma exchange; SMT, standard medical treatment. PLEX, Plasma exchange; SMT, standard medical treatment. This landmark RCT (Larsen et al.3Larsen F.S. Schmidt L.E. Bernsmeier C. et al.High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial.J Hepatol. 2016 Jan; 64: 69-78Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar) showed ∼ 10% increase in survival in ALF patients who had high volume PLEX compared to SMT, among those who did not have urgent liver transplantation. The patients studied had multiple etiologies for ALF; paracetamol overdose was the predominant cause. Two points can be highlighted in this study. First, this study provides high quality evidence that compared to SMT; PLEX improves survival in ALF patients. Based on the results of this study, American Society for Apheresis now recommends high volume PLEX as a stand-alone treatment for ALF.25Padmanabhan A. Connelly-Smith L. Aqui N. et al.Guidelines on the use of therapeutic Apheresis in clinical practice - evidence-based approach from the writing committee of the American society for Apheresis: the eighth special issue.J Clin Apher. 2019 Jun; 34: 171-354Crossref PubMed Scopus (759) Google Scholar Second, of 183 ALF patients in this study (conducted in three developed countries from 1998 to 2010), only 90 patients (49%) were listed for urgent liver transplantation and only 56 patients (62%) of those listed subsequently had liver transplantation. Also, 64 patients who met poor prognostic criteria and thus merited liver transplantation, were not listed for transplantation due to contraindications (like severe psychiatric or medical co-morbidities). Thus, 127/183 study patients (69%) did not undergo urgent liver transplantation. This highlights the need for non-transplant treatments for ALF. In this study, 40 consecutive ALF patients with cerebral edema (noted on computed tomography brain) were randomised to standard volume PLEX or SMT.5Maiwall R. Bajpai M. Singh A. et al.Standard-volume plasma exchange improves outcomes in patients with acute liver failure: a randomized controlled trial.Clin Gastroenterol Hepatol. 2022 Apr; 20: e831-e854Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar The predominant cause of ALF was hepatotrophic viruses (78%) (hepatitis E: 14 patients, hepatitis A: 12 patients, hepatitis B: 5 patients). Better transplant-free survival at 21 days was noted in PLEX-treated patients (75% survived) than SMT patients (45% survived) (P = 0.04, hazard ratio [HR] 0.30, 95% CI 0.01–0.88). PLEX independently predicted survival (HR, 0.33; 95% CI, 0.11–0.98; P = 0.045) after adjusting for King's College hospital criteria for urgent liver transplantation. PLEX treatment resulted in greater amelioration of Systemic Inflammatory Response Syndrome (SIRS) and reduction in Sequential Organ Failure Assessment (SOFA) scores than SMT. The investigators presented data suggesting that the improved survival with PLEX was possibly caused by reduction in cytokine storm and ammonia levels. In this study of 37 children with ALF caused by Wilson's disease (median age 9 years, 62% males), 19 children had high volume PLEX and 18 children had SMT.4Pawaria A.
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