Evaluation of Biomarkers to Quantify Liver Pathology in Patients With Presumed Non-Alcoholic Steatohepatitis at Baseline and Following Bariatric Surgery

Inclusion Criteria:

- Age ≥18 years

- Undergoing bariatric surgery (Roux-en-Y or gastric sleeve only) as part of clinical
care.

- Negative human chorionic gonadotropin (hCG) level (female participants who become
pregnant during the study will be withdrawn)

- For nonalcoholic steatohepatitis (NASH) participants - FibroScan: Controlled
Attenuation Parameter (CAP) 290 db/m and Vibration-Controlled Transient Elastography
(VCTE) 8 kilopascal (kPa). For participants who meet FibroScan criteria, inclusion
will require MRI-PDFF ≥8%; MRE: ≥2.7 kPa.

- For NAFLD or normal participants - FibroScan: No requirement for minimum CAP level and
VCTE <7 kPa. For participants that meet the FibroScan criteria- no requirement for
minimum MRI-PDFF; MRE ≤ 2 kPa.

- Histopathology assessment of liver biopsy that confirms NASH diagnosis

- Hemoglobin A1c (HbA1c) ≤ 9.5%

- Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)

- Body mass index (BMI) ≥ 35 kg/m2

- Able to speak and understand written and spoken English

- Understands the procedures and agrees to participate by giving written informed
consent

- Willing and able to comply with scheduled visits, laboratory tests, and other study
procedures

Exclusion Criteria:

- Participation in other studies involving investigational drug(s) within 30 days prior
to Screening Visit 1

- History of regular alcohol consumption exceeding 14 drinks/week for females or 21
drinks/week for males within the previous 6 months

- A total score of 8 on the Alcohol Use Disorders Identification Test questionnaire
(Appendix B), indicating harmful or hazardous ethanol consumption

- A positive urine drug test for illicit drugs

- Clinical evidence of hepatic decompensation, including, but not limited to esophageal
varices, ascites, or hepatic encephalopathy

- Evidence of other forms of chronic liver disease (including laboratory tests as
assessed by a sponsor-identified laboratory, and confirmed with a single repeat, if
needed): Hepatitis B virus (HBV): defined by presence of hepatitis B surface antigen
(HBsAg); Hepatitis C virus (HCV): As defined by a clinical history of previous
diagnosis of Hepatitis C (treated or untreated) or a positive Hepatitis C antibody
(HCVAb); Known diagnosis of primary biliary cirrhosis, primary sclerosing cholangitis,
autoimmune hepatitis, or overlap syndrome; Alcoholic liver disease; Known diagnosis of
hemochromatosis; Prior known drug-induced liver injury; Known or suspected
hepatocellular carcinoma (HCC) or other liver cancer; History of liver transplant,
current placement on a liver transplant list, or current model of end-stage liver
disease (MELD) score >12; Histological presence of cirrhosis on a prior biopsy.

- Human Immunodeficiency Virus (HIV) infection, defined as presence of HIV antibody

- Diagnosis of type 1 diabetes mellitus

- Any malignancy not considered cured, except basal cell carcinoma and squamous cell
carcinoma of the skin (a subject is considered cured if there has been no evidence of
cancer recurrence in the previous 5 years)

- Use of drugs historically associated with non-alcoholic fatty liver disease (NAFLD)
for 1 month in the previous year prior to Visit 3 (day of Surgery); examples include:
amiodarone, methotrexate, systemic glucocorticoids, tetracyclines, tamoxifen,
estrogens at doses greater than those used for hormone replacement, anabolic steroids,
valproic acid, other known hepatotoxins

- Subjects with history of severe claustrophobia impacting ability to perform MRI during
the study without mild sedation/treatment with an anxiolytic

- Subjects who fulfill any of the contraindications for MRI; examples include metal
implants, devices, paramagnetic objects contained within the body and excessive or
metal-containing tattoos

- Unable to participate in MR assessments due to physical limitations of equipment
tolerances (MRI bore size and 500-pound weight limit) based on Investigator's judgment
at screening

- Any person unable to lie still within the environment of the MRI scanner or maintain a
breath hold for the required period to acquire images without mild sedation/treatment
with an anxiolytic

- Subjects with any anatomical or pathological abnormality that would either preclude or
tend to confound the analysis of study data, including any clinically significant
abnormal findings on the MRI obtained at Screening Visit 2.

- Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
within 56 days prior to Screening Visit 1 (participants may not donate blood any time
during the study, through the final study visit)

- Known history or suspected hypersensitivity to human serum albumin, or its
preparations.

- Investigator site staff members directly involved in the conduct of the study and
their family members, site staff members otherwise supervised by the investigator, or
subjects who are Pfizer employees, including their family members, directly involved
in the conduct of the study