Elucidating Shared Mechanisms Contributing to NAFLD and PsA Disease Severity With Guselkumab Therapy

1. Adults with diagnosis of PsA fulfilling the classification for PsA (CASPAR) criteria.
2. Must have:

1 or more swollen joint(s) and/or one or more active sites of enthesitis

1. AND/OR

1 or more psoriatic plaques

1. No changes in the regular medication regimen within the last three months, and no use of systemic and/or chronic steroids within 8 weeks leading up to the study.
2. Overweight or obese by BMI ≥ 25.0 kg/m2 or ≥ 23.0 for Asian participants
3. Patients are starting Guselkumab therapy for PsA as indicated by primary rheumatologist
4. Elevated liver fat on controlled attenuation parameter (CAP) ≥ 288 dB/m, which is consistent with NAFLD after exclusion of secondary causes of liver disease.

1. Patients with prior exposure to IL12/23i, IL-17i, JAKi, or TYK2i. Patients with exposure to more than 2 TNFi.
2. Evidence of other causes of chronic liver disease
   • 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 Abin 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.
   • Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
   • Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.
   • Drug-induced liver disease as defined on the basis of typical exposure and history.
   • Bile duct obstruction as shown by imaging studies.
   • History of gastrointestinal bypass surgery or ingestion of medications known to produce steatosis, such as corticosteroids, high-dose estrogen, tamoxifen, amiodarone or tetracycline in the previous 6 months.
   • 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
   • Presence of regular and/or excessive use of alcohol (defined as >30g/day for males and >15g/day for females) for a period longer than 2 years at any times in the last 10 years
   • Serum creatinine > 2.0 mg/dL
   • The subject is a pregnant or nursing female or is planning to become pregnant
   • Life expectancy less than 5 years
3. History of known HIV infection