Clinical Research Directory

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 acquired aplastic anemia at presentation * Organ dysfunction assessment defined below: * Renal dysfunction: eGFR \< 30 mL/min/1.73m² or * Mechanical Ventilation * Persistent systemic infection despite appropriate antimicrobial therapy * Active infection with Hepatitis A, B, C, HIV, or herpes simplex virus * Active mycobacteria (typical and atypical), Histoplasma Capsulatum, Herpes zoster infections. * Patients with positive respiratory viral infection, including adenovirus, rhinovirus/enterovirus, SARS-CoV-2, influenza, and respiratory syncytial virus, only if they also have declining respiratory function needing positive pressure support. Suspected primary hemophagocytic lymphohistiocytosis based on patients with a history of consanguinity and/or central nervous system dysfunction or other clinical manifestations that is exaggerated compared to the degree of liver dysfunction (as judged by the site investigator and study team) * Diagnosis of Autoimmune Hepatitis, Wilson Disease, inborn error of metabolism, acute drug or toxin-induced liver injury, or ischemic liver injury * History of severe hypersensitivity or allergy to any component of this study regimen * History of confirmed malignancy * History of recreational drug use within the past 4 weeks, excluding cannabinoids * Therapy with an immunosuppressive agent or an experimental drug within the past 6 weeks * Pregnant, planning to become pregnant during study window, or breastfeeding at time of study entry * Patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method (e.g. hormonal contraceptives, intrauterine device, or double-barrier method) for the duration of their study participation. Patients must maintain adequate contraception for at least 4 weeks after their last dose of emapalumab. * Live-virus vaccination within 4 weeks of study entry or anticipated need for a live or live attenuated vaccine within 4 weeks after the last dose of emapalumab * Peceived Bacillus Calmette-Guerin vaccine within 12 weeks prior to screening * Patient or parent/guardian unable to give informed consent or unable to comply with the treatment protocol * Prisoners will be excluded