Semaglutide Treatment in the Real-world for Fibrosis Due to NAFLD in Obesity and T2DM

Prior treatment

• Evidence of cirrhosis or previously known cirrhosis, based on the results from previous liver biopsy or history of portal hypertension presented by ascites, hepatic encephalopathy or varices
• Use of other weight loss medications, including GLP1RA within the last 90 days
• Greater than 10% weight loss in the prior six months

Other illness

• Known or suspected hypersensitivity to GLP1RA medications including semaglutide
• History of bariatric surgery within the past 5 years or expected bariatric surgery

Lab values

• Platelet count ≤ 140,000 per Ml
• Albumin \< 3.6 g/dL
• INR \> 1.35, unless on coumadin for another indication
• Serum creatinine \> 2.0 mg/dL
• eGFR \< 30 mL/min/1.73 m² as defined according to the CKDEPI creatinine equation⁷⁰
• Evidence of other causes of chronic liver disease including:
  • Hepatitis B, as defined as presence of hepatitis B surface antigen (HBsAg).
  • Previous or current infection with Hepatitis C, as defined by presence of hepatitis C virus Ab in serum (anti-HCV Ab).
  • Autoimmune hepatitis, as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
  • Autoimmune cholestatic liver disorders, as defined by elevation of alkaline phosphatase and anti- mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis.
  • Wilson disease, as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease deficiency, as defined by alpha-1-antitrypsin phenotype and liver histology consistent with alpha-1-antitrypsin deficiency.

Other

• Presence of regular and/or excessive use of alcohol, defined as \> 30 g/day for males and \> 20 g/day for females, for a period longer than 2 years at any time in the last 10 years
• VCTE ≥ 20 kPa

• Adult, age ≥ 40 and \< 80 years
• Participant must meet at least one of following sets of conditions:
  • BMI ≥ 27 kg/m² OR
  • BMI ≥ 25 kg/m² AND presence of i) pre-diabetes (HbA1C ≥ 5.7) or ii) type 2 diabetes mellitus (T2DM), as defined by the American Diabetes Association (ADA) clinical practice recommendations.
  • The ADA definition of T2DM is applicable if one of the following criteria is met:
  • Presence of diabetes symptoms (polyuria, polydipsia, polyphagia, increased fatigue, weight loss, blurred vision) and casual plasma glucose ≥ 200 mg/dL (11.1 mmol/L)
  • Fasting plasma glucose (FPG) ≥ 126 mg/dl (7.0 mmol/L)
  • Plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test (OGTT)⁶⁸. If any of the above test results occur, testing should be repeated on a different day to confirm the diagnosis.
  • OR
  • Hemoglobin A1C (HbA1C) ≥ 6.5% ⁶⁹.
• FAST score ≥ 0.5 and VCTE ≥ 8.0 kPa; FAST score threshold based on data from MAESTRO-NASH trial⁴²; VCTE cutpoint based on AASLD guidelines for identification of patients with significant fibrosis risk.
• Participants without a VCTE assessment in their medical record may qualify for the study if they have a FIB-4 ≥ 1.0, which is a cutpoint based on observations of patients with T2DM in Ajmera et al³⁰, and VCTE ≥ 8.0 kPa.
• The subject is fully informed and willing and able to perform all the procedures specified in the protocol and has signed a written informed consent to participate