Fenofibrate for Compensated Cirrhosis Patients With Primary Biliary Cholangitis

Prior treatment

• History or presence of other concomitant liver diseases.
• Taking hepatotoxic drugs (e.g., dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than 2 weeks within 6 months, and long-term hormonal users.
• Currently using statins (such as pravastatin, fluvastatin, and simvastatin), other fibrates (such as gemfibrozil and bezafibrate), and drugs structurally similar to fenofibrate (like ketoprofen).
• Planned to receive an organ transplant or an organ transplant recipient.
• Needing Liver transplantation within 1 year according to the Mayo Rick score.

Other illness

• Allergic to fenofibrate or ursodeoxycholic acid.
• Recurrent variceal bleeding, poorly controlled hepatic encephalopathy or refractory ascites.
• Patients with a history of severe cardiac, cerebrovascular, renal, respiratory disease or functional failure, and psychiatric disorders (including those due to alcohol and drug abuse).
• Any other condition(s) that would compromise the safety of the subject or compromise

Lab values

• ALT or AST \> 5×ULN, TBIL \> 3×ULN.
• If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
• Creatinine \>1.5×ULN and creatinine clearance \<60 ml/min.

• Must have provided written informed consent
• Age 18-75 years;
• BMI 17-28 kg/m2
• Male or female with a diagnosis of PBC, by at least two of the following criteria:
  • History of AP above ULN for at least six months;
  • Positive AMA titers (\>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies;
  • Documented liver biopsy result consistent with PBC.
• Diagnosis of compensated cirrhosis, as demonstrated by the presence of ≥ 1 of the following 4 diagnostic factor
  • The histology was consistent with the diagnosis of liver cirrhosi;
  • Endoscopy shows esophageal and gastric varices or ectopic varices of digestive tract, excluding non cirrhotic portal hypertension;
  • Ultrasound or CT and other imaging examinations indicate the characteristics of liver cirrhosis or portal hypertension, such as splenomegaly, portal vein ≥ 1.3 cm, or liver stiffness measured by transient elastography\>16.9 kPa;
  • Abnormal laboratory inspection indicators (2 out of 4): 1) PLT \< 100 × 109/L, and no other reason can be explained; 2) Serum albumin\<35 g/L, excluding malnutrition or kidney disease and other causes; 3) INR \> 1.3 or PT prolongation (stop thrombolytic or anticoagulant drugs for more than 7 days); 4) AST/PLT (APRI)\>2）
• Incomplete response to UDCA defined by ALP \> 1.67 x ULN
• Taking UDCA for at least 6 months (stable dose for ≥ 3 months) prior to Day 0