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ALF (ALF) is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) hepatic encephalopathy, and (3) absence of a prior history of liver disease.
Interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) to 24 weeks (AASLD-ALF study group). Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI ≤ 7 day), acute (IEI ≤ 4 weeks) and sub-acute ALF (IEI ≥ 5 week to ≤12 weeks) by British authors.
Since the 1960s, Liver Transplantation (LT) has emerged as a cornerstone intervention to cure liver failure. Mortality in patients with liver failure who cannot be rescued with Liver Transplantation remains high despite improvements in supportive care.
Artificial Liver Support System (ALSS) in ALF aim to remove excess inflammatory cytokines and attenuate inflammatory response, to remove albumin-bound and water-soluble toxins, to restore and preserve hepatic function and mitigate or limit the progression of multiorgan failure while hepatic recovery or liver transplant occurs. ALSS may also provide benefit in instances where LT is contraindicated.
The following beneficial effects have been documented with ALSS in ALF patients: improvement of jaundice, amelioration of hemodynamic instability, improvement of hepatic encephalopathy, SOFA score and survival.
HA 330-II is a broad-spectrum adsorbent made of neutral macroporous resin, removes toxins such as Inflammatory mediators (IL-1, IL-6, IL-8 & TNF-α) along with hepatic toxins such as phenol, mercaptan, aromatic amino acids, false neurotransmitters and indirectly ammonia by improving liver function recovery. However, this indirect ammonia removal with HA 330-II is insignificant. By removing excess inflammatory cytokines and attenuating uncontrolled immune response, HA 330-II prevents worsening of encephalopathy, improves liver function recovery and improves prognosis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Hemoperfusion treatment with HA 330-II | Experimental | Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with SMT as per patients requirement. |
|
| Standard medical treatment (SMT) | Active Comparator | SMT as per patients requirement- Management of cerebral edema/intracranial hypertension: prophylactic antibiotics, administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure, volume replacement and pressor support (noradrenaline, doubutamine, dopamine) as needed, NAC and correction of metabolic parameters. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HA 330-II | Device | One unit for 2-4 hours treatment, for 3 consecutive days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of HA 330-II to prolong liver-transplantation free survival. | The length of survival time after first hemofiltration treatment during the follow-up period. | Up to 30 Days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Systemic inflammatory response syndrome (SIRS) score. | To assess efficacy of treatment. | Up to 7 Days, post hemofiltration |
| Change in Acute Physiology and Chronic Health Evaluation (APACHE-II) score. |
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Inclusion Criteria:
• Acute Liver Failure patients with SIRS and Hepatic Encephalopathy, without hyperbilirubinemia.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mithun Sharma, MD, DM | Contact | 08790622655 | drmithunsharma@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Mithun Sharma | AIG Hospitals | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asian Institute Of Gastroenterology | Recruiting | Hyderabad | Telangana | 500032 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11003617 | Background | Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R. The systemic inflammatory response syndrome in acute liver failure. Hepatology. 2000 Oct;32(4 Pt 1):734-9. doi: 10.1053/jhep.2000.17687. | |
| 26785141 | Background | Lee KC, Stadlbauer V, Jalan R. Extracorporeal liver support devices for listed patients. Liver Transpl. 2016 Jun;22(6):839-48. doi: 10.1002/lt.24396. |
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| ID | Term |
|---|---|
| D065290 | Acute-On-Chronic Liver Failure |
| ID | Term |
|---|---|
| D017114 | Liver Failure, Acute |
| D017093 | Liver Failure |
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
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Hemoperfusion treatment with HA 330-II, one unit for 2-4 hours treatment, for 3 consecutive days along with standard medical treatment (SMT) as per patients requirement.
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| Standard medical treatment (SMT) | Drug | SMT as per patients requirement- Management of cerebral edema/intracranial hypertension: prophylactic antibiotics, administration of mannitol or 3% saline for severe elevation of Intra Cranial Pressure, volume replacement and pressor support (noradrenaline, doubutamine, dopamine) as needed, NAC and correction of metabolic parameters. |
|
To assess efficacy of treatment.
| Up to 7 Days, post hemofiltration |
| Change in sequential organ failure assessment (SOFA) score. | To assess efficacy of treatment. | Up to 7 Days, post hemofiltration |
| Change in chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score. | To assess efficacy of treatment. | Up to 7 Days, post hemofiltration |
| 26325537 | Background | Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, Triantafyllou E, Bernal W, Auzinger G, Shawcross D, Eefsen M, Bjerring PN, Clemmesen JO, Hockerstedt K, Frederiksen HJ, Hansen BA, Antoniades CG, Wendon J. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol. 2016 Jan;64(1):69-78. doi: 10.1016/j.jhep.2015.08.018. Epub 2015 Aug 29. |
| D004066 |
| Digestive System Diseases |