Efficacy and Safety of the Extracorporeal Liver Assist Device (ELAD) in Acute on Chronic Hepatitis

Inclusion criteria

• Age >/= 18</= 67 years; AND
• Acute decompensation of chronic liver disease over the preceding 30 days; AND
• MELD score between 18 and 35, inclusive; AND
• Subject or designated representative must provide Informed Consent

Exclusion criteria

• Platelets <50,000mm at baseline; OR
• Evidence of chronic renal failure as defined by a serum creatinine >/= 2.5mg/dL as measured during the 1-6 month period prior to study entry. (Subject is not excluded with a creatinine >2.5 mg/dL if deemed to be type-1 hepato-renal syndrome); OR
• Contraindication to renal replacement therapy (hemodialysis or hemofiltration); OR
• International Normalization Ratio (INR) > 3.5; OR
• Septic shock as defined by a positive blood culture and two or more of the following:

• Systolic blood pressure <90mmHg OR mean arterial pressure <60mmHg;
• Tachypnea > 20 breaths per minute OR a PaCO2<32 mmHg;
• White blood cell count < 4000 cell/mm3 OR > 12000 cell/mm3 (<4 x 10(9) or >12 x 10(9) cells/L).
• Evidence of major hemorrhage as indicated by:

• requiring >/= 4 units packed red blood cells within a 48 hour period prior to Screening, OR
• hemodynamic instability (sustained pulse > 120 beats/min AND systolic blood pressure < 100 mmHg over one hour)

Subjects with a recent history of gastrointestinal hemorrhage who have been successfully treated and remain hemodynamically stable for a period of 48 hours will then be eligible for the study if the investigator determines the subject to be at low risk for rebleeding; OR

• Evidence (by physical exam, history or lab evaluation) of significant concomitant disease including chronic congestive heart failure, vascular disease, emphysema, AIDS, hepatitis due to herpes virus, Wilson's disease, or Budd-Chiari syndrome; OR
• Known history of hepatocellular carcinoma beyond the Milan criteria and/or portal vein thrombosis; OR
• Evidence of spontaneous bacterial peritonitis with uncontrolled infection; OR
• Evidence of brain death as determined by blood flow studies positive for herniation AND/OR absence of pupillary reflex; OR
• Systolic blood pressure <85 mmHg OR MAP <50mmHg at baseline; OR
• Requirement for escalating doses of vasopressor support OR of an alpha-adrenergic agent for one hour or longer AND evidence of hemodynamic instability; OR
• Subject at maximum vasopressor dose at Screen; OR
• Clinical or radiographic evidence of a new stroke or intracerebral bleeding; OR
• Seizures uncontrolled by medication; OR
• Acute myocardial infarction based on clinical and/or electrocardiographic evidence; OR
• Lung disease defined by a PaO2<60mmHg on room air, acute respiratory distress syndrome, or a history of severe COPD or interstitial lung disease; OR
• Pregnancy as determined by beta-HCG results or lactation; OR
• Participation in another investigational drug, biologic, or device study within 1 month of enrollment. Subjects enrolled in an observational study will be eligible for this trial.
• Previous liver transplant.
• Previous participation in a clinical trial involving ELAD.