The Safety and Efficacy of Upadacitinib in Refractory Autoimmune Related Cholangitis and Atopic Dermatitis With Moderate to Severe Itching

Inclusion Criteria Patients must meet all of the following criteria to be eligible for enrollment: 1. Aged ≥18 and ≤70 years, of either sex. 2. Criteria for Atopic Dermatitis (AD) Diagnosis of AD according to the Chinese diagnostic criteria for adult AD, defined as meeting the primary criterion (a) plus either criterion (b) or (c) below: 1. Presence of symmetrical eczema with a disease duration of more than 6 months. 2. Personal and/or first-degree family history of atopic diseases (e.g., eczema, allergic rhinitis, asthma, allergic conjunctivitis, etc.). 3. At least one of the following laboratory findings: elevated serum total immunoglobulin E (IgE), elevated peripheral blood eosinophil count, or positive allergen-specific IgE. Presence of moderate-to-severe pruritus, defined as a Visual Analogue Scale (VAS) score ≥4. 3. Criteria for Primary Biliary Cholangitis (PBC) Diagnosis of PBC according to practice guideline criteria, defined as meeting at least two of the following three criteria: 1. Biochemical evidence of cholestasis, primarily elevated alkaline phosphatase (ALP) and/or gamma-glutamyl transferase (GGT). 2. Positivity for anti-mitochondrial antibody (AMA) or AMA-M2, or positivity for other disease-specific autoantibodies (anti-gp210 or anti-sp100 antibodies). 3. Histological evidence of non-suppurative destructive cholangitis and small bile duct destruction. Patients must have received a standard regimen of ursodeoxycholic acid (UDCA) for ≥12 months (at a dose of no less than 13-15 mg/kg/day) in combination with at least two subsequent-line therapies (including Farnesoid X receptor agonists, peroxisome proliferator-activated receptor agonists, budesonide, or other immunosuppressants) for ≥3 months. At screening, ALP ≥1.5 × upper limit of normal (ULN) or GGT ≥5 × ULN. 4. Criteria for Primary Sclerosing Cholangitis (PSC) For large-duct PSC, diagnosis must meet the following criteria: 1. Biliary imaging showing characteristic multifocal, short-segmental, or annular strictures involving both intra- and extrahepatic bile ducts. 2. At least one of the following clinical manifestations: biochemical evidence of cholestasis (primarily elevated ALP and/or GGT); clinical or histological evidence of coexisting inflammatory bowel disease (IBD); or liver histology showing periductal inflammation with fibrosis (i.e., periductal "onion-skin" appearance). 3. Exclusion of secondary sclerosing cholangitis due to other etiologies. For small-duct PSC, diagnosis must meet the following criteria: 1. Biochemical evidence of cholestasis with no significant abnormalities on recent biliary imaging. 2. Liver histology showing typical PSC changes as described above (periductal inflammation with fibrosis / "onion-skin" appearance). 3. Exclusion of other causes of cholestasis. Patients must have received a standard regimen of UDCA for ≥3 months (at a dose of no less than 13-15 mg/kg/day). At screening, ALP ≥1.5 × ULN or GGT ≥5 × ULN. Exclusion Criteria Patients who meet any of the following criteria will be excluded from enrollment: 1. Known concurrent or history of other hepatobiliary diseases, including but not limited to: active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; complete biliary obstruction; acute cholecystitis or symptomatic cholelithiasis; suspected or confirmed hepatocellular carcinoma (HCC) or cholangiocarcinoma. 2. Child-Pugh Class C cirrhosis; evidence of end-stage liver disease, including: history of liver transplantation or being on the liver transplant waiting list; Model for End-Stage Liver Disease (MELD) score \>20; severe portal hypertension complications (including severe gastric or esophageal varices, refractory or diuretic-resistant ascites, history of variceal bleeding); or other serious cirrhosis-related complications (spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome). 3. Total bilirubin \>10 × upper limit of normal (ULN). 4. Serum creatinine ≥1.5 × ULN and creatinine clearance \<60 mL/min. 5. Platelet count \<50 × 10⁹/L. 6. International normalized ratio (INR) \>1.5. 7. Serum albumin \<3.0 g/dL. 8. Use of moderate or strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) within 14 days prior to the first dose of study drug or planned use throughout the study period. 9. Presence of diseases that may cause non-hepatic elevation of ALP (e.g., Paget's disease of bone) or any condition with an anticipated life expectancy of less than 2 years. 10. Known drug abuse or alcohol abuse within 6 months prior to the first dose of study drug, defined as weekly alcohol consumption exceeding 14 standard drinks (1 standard drink equivalent to 360 mL beer, 45 mL of 40% distilled spirits, or 150 mL wine). 11. Unstable concomitant diseases or use of concomitant medications that cannot be maintained on a stable regimen throughout the clinical study period. 12. Pregnant women, women planning to become pregnant, breastfeeding women, or fertile patients (male or female) who are unwilling to use at least one effective method of contraception from the time of signing informed consent until 30 days after the last dose of study drug. 13. Participation in any other interventional clinical trial and receipt of any investigational product within 3 months prior to the first dose of study drug. 14. Positive results for human immunodeficiency virus antibodies (HIV Ab) or Treponema pallidum antibodies (TP Ab). 15. Any other condition that, in the investigator's judgment, would preclude the patient's participation in this study.