Inclusion Criteria:

1. Signed informed consent
2. Age ≥ 18 years
3. UDCA treatment for at least 6 months prior to inclusion
4. Liver biopsy compatible with PBC
5. Liver biopsy performed within the last 6 months prior to inclusion

6. PBC patients at risk of disease progression based on one or more of the following criteria:

   • Serum alkaline phosphatase ≥ 3 times the upper limit of normal at any time since diagnosis of PBC and ALT ≥ 2 times upper limit of normal or
   • Total Bilirubin ≥ 1.0 mg/dl (≥ 17 µmol/L) or
   • Moderate to severe periportal or periseptal lymphocytic interface hepatitis or
   • Periportal and portal fibrosis with numerous septa (Ludwig stage III) without cirrhosis
7. Type 2 anti-mitochondrial antibodies > 1:40 by direct immunofluorescence
8. Women of child-bearing potential have to apply appropriate contraceptive methods, e.g., hormonal contraception, intrauterine device (IUD), double-barrier method of contraception (e.g., use of a condom and spermicide), partner has undergone vasectomy and subject is in monogamous relationship. The investigator is responsible for determining whether the subject has adequate birth control for study participation

Exclusion Criteria:

1. Histologically proven cirrhosis
2. Positive Hepatitis B or C serology
3. Positive HIV serology
4. Primary Sclerosing Cholangitis
5. Wilson's-Disease
6. Celiac Disease (blood tests and/or oesophago-gastro-duodenoscopy with histological examination to be performed)
7. α1-anti-Trypsin-deficiency
8. Haemochromatosis
9. Autoimmune-Hepatitis (AIH; defined by an Alvarez score > 15 without treatment or ≥ 17 with treatment); Note: PBC/AIH overlap disease, treated insufficiently with UDCA monotherapy may be enrolled
10. Treatment with any of the following drugs within the last 3 months prior to inclusion: colchicine, corticosteroids, azathioprine or other immunosuppressive drugs (e.g. cyclosporine, methotrexate), chlorambucil, D-penicillamine, fibrates, or antihyperlipidemic drugs
11. Treatment with ketoconazole or other CYP3A inhibitors within the last 4 weeks before baseline; rifampicin (up to 600 mg/d) is allowed to treat pruritus until baseline
12. Sonographic or endoscopic signs of portal hypertension
13. Ascites or history of ascites
14. Hepatic encephalopathy or history of hepatic encephalopathy
15. Total bilirubin > 3.0 mg/dl (> 50 µmol/L)
16. Albumin < 36 g/L
17. Prothrombin ratio < 70%
18. Platelet count < 135.000/mm3
19. Osteoporosis proven by bone densitometry
20. Diabetes mellitus, defined as B-Glucose > 125 mg/dl on an empty stomach (even when controlled)
21. Hypertension, defined as persistent raised blood pressure > 140/90 mmHg
22. Suspected non-compliance of the patient (suspected difficulties to comply with the study period of 36 months)
23. Severe co-morbidity substantially reducing life expectancy
24. Known intolerance/hypersensitivity/resistance to study drugs or drugs of similar chemical structure or pharmacological profile
25. Existing or intended pregnancy or breast-feeding
26. Participation in another clinical trial within the last 30 days, simultaneous participation in another clinical trial, or previous participation in this trial