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

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.