Safety and Efficacy of the ELAD System (ELAD) to Treat Acute Liver Failure (ALF)

Inclusion Criteria: 1. Weight ≥ 40 kg; 2. Age ≥ 18; 3. Diagnosis of ALF attributed to one of the following: 1. FHF (acute liver failure with no preexisting liver disease, see below); 2. Primary Graft Non-Function (PNF); 3. Surgically-Induced Liver Failure (including subjects with small for size liver transplants, living donor liver transplants, and subjects with risk of ALF following liver cancer surgery); 4. Subjects must not be listed for transplant at the time of Enrollment or, if listed, in the opinion of the Investigator are unlikely to be transplanted within 72 hours; 5. Subject or legally authorized representative must provide Informed Consent for VTI-212 and the Follow-up Registry VTI-212E. Subjects with FHF must meet one of the following criteria: 6. Known acetaminophen ingestion or diagnostic serum level, and at least one of the following: 1. Prothrombin time (PT) \> 100 seconds \[International Normalized Ratio (INR) \> 6.5\], OR 2. Encephalopathy Grade 3 or 4 AND ARTERIAL AMMONIA \>100 umol/liter and at least one of the following: i. Arterial pH \< 7.30 at ≥ 24 hours after drug ingestion or volume resuscitation; ii. Renal failure documented by urine output \< 0.5 mL/kg/hr over the preceding 12 hours; iii. Creatinine \> 2.5 mg/dL; OR 7. Non-acetaminophen-induced FHF with Encephalopathy Grade 3 or 4 and arterial ammonia \>100 umol/liter, and at least two of the following: 1. Viral Hepatitis (other than A, B or C) or drug (non-acetaminophen)-induced FHF 2. Serum bilirubin \> 17 mg/dL 3. Subject \> 40 years old 4. PT \> 50 seconds (INR \> 3.5) 5. Jaundice to encephalopathy time ≥ 7 days Exclusion Criteria: 1. Cerebral Perfusion Pressure ≤40 mm Hg for 1 hour or longer as measured by an intracranial pressure (ICP) monitor. (NOTE: In those cases where ICP monitor placement cannot be performed prior to study enrollment, this exclusion criterion will not apply); 2. Chronic liver disease (e.g., compensated cirrhosis of any etiology, chronic hepatitis, nonalcoholic steatohepatitis, cholestatic liver disease, or metabolic liver disease) (NOTE: steatosis is not an exclusion criterion); 3. Acute clinical symptoms that, in the Investigator's opinion, are likely to result in death within 48 hours of enrollment; 4. Evidence of infection unresponsive to antibiotics (e.g. increased tissue involvement relative to initial diagnosis, clinical worsening of symptom) indicated by any of the following: 1. Presence of sepsis or septic shock; OR 2. Positive blood cultures (bacteremia, fungemia) within 72 hours prior to Enrollment; OR 3. Presence of spontaneous bacterial peritonitis during the 2 days prior to Enrollment; OR 4. Clinical and radiological signs of pneumonia. 5. Concomitant disease including chronic congestive heart failure, severe vascular disease, emphysema, AIDS, cancer (except non-melanoma skin cancer), acute fatty-liver disease, hepatitis due to herpes virus or Budd-Chiari syndrome. (NOTE: in the case of subjects enrolled due to surgery-induced liver failure (SILF) then the original cause for the surgery will not be a criterion for exclusion); 6. Portal hypertension; 7. Liver dysfunction due to trauma; 8. Irreversible brain death; 9. Platelet count \< 30,000/mm3 \[NOTE: Subject may be included at the physician's discretion if platelet count exceeds 30,000/mm3 at time of initiation of therapy (even if the value is following platelet transfusion) and can be managed through the administration of blood products\] 10. Cardiovascular sepsis-related organ failure assessment score (SOFA score) \>3; 11. Stroke or intracranial hemorrhage; 12. Seizures uncontrolled by medication; 13. Acute myocardial infarction; 14. Lung disease defined by a partial pressure of oxygen measurement (PaO2) ≤60 mmHg or a fraction of inspired oxygen (FiO2) ≥0.6, not corrected by medical management \[including continuous venovenous hemofiltration (CVVH) if indicated\] and ventilation with a Positive End Expiratory Pressure (PEEP) of \>8cm H2O; 15. Acute Respiratory Distress Syndrome; 16. Pregnancy as determined by beta-human chorionic gonadotropin (β-hCG) results; 17. ≤ 2 weeks postpartum; 18. Participation in another investigational drug, biologic, or device study within one month of enrollment, except for observational studies (the observational study setting should not affect the safety and/or efficacy of the VTI-212 clinical trial); 19. Prior ELAD therapy; 20. Has a Do Not Resuscitate or a Do Not Intubate (DNR/DNI) directive (or local equivalent) or any other Advanced Directive limiting Standard of Care in place (the DNR/DNI criterion is not applicable in the UK).