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

Inclusion criteria

• Adults with diagnosis of PsA fulfilling the classification for PsA (CASPAR) criteria.
• Must have:
• or more swollen joint(s) and/or one or more active sites of enthesitis
• \. AND/OR
• or more psoriatic plaques
• \. 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.
• \. Overweight or obese by BMI ≥ 25.0 kg/m2 or ≥ 23.0 for Asian participants
• \. Patients are starting Guselkumab therapy for PsA as indicated by primary rheumatologist
• \. Elevated liver fat on controlled attenuation parameter (CAP) ≥ 288 dB/m, which is consistent with NAFLD after exclusion of secondary causes of liver disease.

Exclusion criteria

• Patients with prior exposure to IL12/23i, IL-17i, JAKi, or TYK2i. Patients with exposure to more than 2 TNFi.
• 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
• History of known HIV infection