Milk Thistle Clinical Trial in Pediatric NAFLD

Inclusion Criteria:

Subjects between the age of 9 to 22 years old diagnosed with non-Alcoholic Fatty Liver Disease (NAFLD) based on current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Guidelines:

• a. Elevated ALT levels greater than 2 times the sex specific upper limit of normalat baseline; (for boys ALT greater than 50 U/L, and girls ALT greater than 44 U/L)i. AND either overweight (with risk factors as noted below) or obese children:

1. In children, obesity is defined as BMI greater than or equal to 95thpercentile in weight and overweight is defined as greater than or equal tothe 85th percentile to less than the 95th percentile.

2. Risk factors associated with overweight child that warrant screening andinclusion are:a. Central obesity, Family history of NAFLD/non-alcoholicsteatohepatitis(NASH), pre-diabetic or diabetic, dyslipidemia, sleep apnea)

3. For participants 18 years or older: Obesity is defined as BMI greater thanor equal to 30 kg/m2; overweight is defined as BMI greater than or equalto 25 kg/m2 and less than 30 kg/m2.

• b. Evidence of Sonographic presence of hepatic steatosis with greater than 5%steatosis on Ultrasound or FibroScan [with a controlled attenuation parameter (CAP)score of 238 or greater)] prior to start of trial starting.

• c. (Or) previous findings on Liver Biopsy consistent with NAFLD including hepaticmacro-vesicular steatosis, ballooning degeneration or Mallory Denk Bodies

Contraception Requirements for Enrollment of adult population:

1. Female participants are eligible if the participant is of reproductive potential andhave a negative -serum pregnancy test (beta human chorionic gonadotropin), are notbreastfeeding, and do not plan to become pregnant during the study and agree to usetwo highly effective birth control methods during the study OR if the participant isnot of child-bearing potential (i.e., surgically [bilateral oophorectomy,hysterectomy, or tubal ligation] or naturally sterile [> 12 consecutive monthswithout menses]). Highly effective birth control methods include condoms with spermicide, diaphragmwith spermicide, hormonal and nonhormonal intrauterine device, hormonalcontraception (estrogens stable ≥ 3 months), a vasectomized male partner, or sexualabstinence (defined as refraining from heterosexual intercourse), from screening,throughout the study, and for at least 30 days after the last dose of study drugadministration. Reliance on abstinence from heterosexual intercourse is acceptableonly if it is the patient's habitual practice.

2. Male patients who are sexually active with a partner of child-bearing potential musteither be sterile (vasectomy with history of a negative sperm count at least 90 daysfollowing the procedure); practice total abstinence from sexual intercourse as thepreferred lifestyle (periodic abstinence is not acceptable); use a male condom withany sexual activity; or agree to use a birth control method considered to beappropriate by the Investigator (such as one of the methods identified above forfemale patients of childbearing potential) from the time of screening until 30 daysafter the last dose of study drug administration. Male patients must agree not todonate sperm for a period of 30 days after the last dose of study drugadministration.

Exclusion Criteria:

1. Patients with cardiovascular disorders (such as history of myocardial infarction,stroke, DVT)

2. Medical conditions including history of malignancy, transplantation, immunologicdiseases (rheumatoid arthritis, inflammatory bowel disease, systemic lupuserythematosus, autoimmune thyroiditis, idiopathic thrombocytopenic purpura,autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis etc.), poorlycontrolled thyroid disease, uncontrolled hypertension.

3. Patients with cirrhosis and hepatic decompensation will be excluded from the study.Hepatic biomarker parameters will be excluded:

• ALT greater than 200 U/L

• AST greater than 200 U/L

• Total bilirubin greater than 2.0 mg/dL

• ALP greater than 500 U/L

• INR greater than 1.4

• GGT greater than 200 U/L

4. Subjects with history or other evidence of severe illness or any other conditionsthat would make the subject, in the opinion of the investigator, unsuitable forparticipation in the trial (such as poorly controlled psychiatric illness).

5. Subjects with unstable diabetes, or HbA1c >9% will be excluded from the study.

6. Subjects who report binge drinking will be excluded from this study.

7. Subjects who partake or state consumption history of tobacco use, vaping, marijuanause, or illicit drug abuse will be excluded from the study.

8. Subjects with severe hepatic dysfunction and synthetic dysfunction withhypoalbuminemia (Albumin < 3.0 g/dL), thrombocytopenia (platelet count <140,000/ml3), or coagulopathy (INR >1.4) will be excluded from the study.

9. Exclude subjects with abnormal renal function characterized as serum creatininegreater than the upper limit of normal range (based on the University of Iowa,Department of Pathology Lab Services Handbook): Pediatric Age Group Premature 0.3 - 1.0 mg/dL Neonates 0.2 - 0.9 mg/dL 2-12 months 0.2 - 0.4 mg/dL 1-2 years 0.2 - 0.5 mg/dL 3-4 years 0.3 - 0.7 mg/dL 5-6 years 0.3 - 0.7 mg/dL 7-8 years 0.2 - 0.6 mg/dL 9-10 years 0.3 - 0.7 mg/dL 11-12 years 0.3 - 0.9mg/dL 13-15 years 0.4 - 0.9 mg/dL Males 16 years and older 0.6 - 1.2 mg/dL Females 16 years and older 0.5 - 1.0 mg/dL

10. Breast feeding women will be excluded from this clinical trial.

11. Subjects who are participating in other drug trials will be excluded fromparticipating.

12. Subjects with a reported or known history of allergy or anaphylactic reaction toRagweed will be excluded from this study.