Severe Hepatitis Intervention With Emapalumab for Liver Disease

Inclusion Criteria (Screening Cohort): * Age: Participants must be ≥ 1 year of age at the time of screening. * Evidence of Severe Hepatic Injury of all etiology (not just iSH/ iSH-T): Serum alanine aminotransferase (ALT) ≥ 1000 U/L documented within 7 days prior to enrollment. Exclusion Criteria (Screening Cohort): * Any condition impairing informed consent/assent or protocol compliance Inclusion Criteria (Intervention Cohort; patients who meet Intervention Cohort eligibility can bypass Screening Cohort enrollment): * Steroid-refractory, steroid-dependent, or relapse of hepatitis after stopping steroids and have an Indeterminate etiology of hepatitis based on standard of care, age appropriate evaluation * Age: ≥ 1 year * ALT ≥ 1000 U/L prior to initiation of any immune modulatory therapy * Evidence of T-cell activation at initial diagnosis, as indicated by one of the following: * sIL2R \> 2× upper limit of normal (ULN) * CXCL9 \> 5× ULN * CD8+ T-cell infiltration in the liver * INR \< 2.0 without evidence of hepatic encephalopathy Exclusion Criteria (Intervention Cohort; patients who meet Intervention Cohort eligibility can bypass Screening Cohort enrollment): * Patients with known Liver failure (defined as INR \>2 on two consecutive occasions without hepatic encephalopathy (HE), or INR ≥1.5 with evidence of HE) * Evidence of chronic liver disease or parenchymal nodularity as demonstrated on imaging (US, CT, or MRI) * Evidence of hepatic encephalopathy * Severe …