Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy

Inclusion Criteria: * Is male or female ≥ 5 years old at baseline. * Is male, female not of childbearing potential, or meets all the following criteria if female of childbearing potential (including perimenopausal women who have had a menstrual period within one year): * Not breastfeeding * Negative pregnancy test result (human chorionic gonadotropin, beta subunit \[βhCG\]) at baseline (not applicable to hysterectomized females). * Must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate when use consistently and correctly, such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner) during the entire duration of metreleptin treatment. * Has physician-confirmed lipodystrophy as defined by evidence of generalized (whole body) or partial (limbs) loss of body fat outside the range of normal variation. * Alcohol consumption of less than 40 grams/week. * A liver ultrasound confirming non-alcoholic fatty liver disease, or previous liver biopsy confirming NASH status. * If ≥ 18 years of age, is able to read, understand and sign the U of M IRBMED approved informed consent form (ICF), communicate with study physician and study team, understand and comply with protocol requirements. * If \< 18 and ≥ 7 years of age, is able to read, understand and sign the appropriate U of M IRBMED approved assent form and has a parent or legal guardian that is able to read, understand and sign the ICF. * If \< 7 and ≥ 5 years of age or unable to read, the appropriate assent form must be explained to the child. * If previously treated with thiazolidinediones or Vitamin E, stable dose of these medications for at least 3 months. Exclusion Criteria: * Presence of advanced liver disease (as evidenced by abnormal synthetic function, abnormal PT or albumin). * Evidence of other etiologies of viral hepatitis. * Presence of clinically significant hematologic abnormalities (such as neutropenia and/or lymphadenopathy). * Presence of HIV infection. * Very poorly controlled diabetes; HbA1c \>10% * Inability to give informed consent. * Presence of ESRD, any type of active cancer, or \>class 2 congestive heart failure ((New York Heart Association Functional Classification System), based on medical history and physical examination. * Active infection (may be transient). * Has known allergies to E. coli-derived proteins or hypersensitivity to any component of metreleptin treatment. * Any other condition in the opinion of the investigators that may impede successful data collection.