Safety and Efficacy of Long-Term Treatment With Atorvastatin in Patients With Primary Biliary Cirrhosis

Study Overview
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Brief Summary
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Primary biliary cirrhosis (PBC) is frequently associated with hypercholesterolemia and possibly with an increased cardiovascular morbidity and mortality. Statins lower serum cholesterol levels and may thus improve the cardiovascular risk in PBC patients. The aim of our study therefore was to prospectively examine the efficacy of low-dose atorvastatin on indicators of cardiovascular risk such as dyslipidemia and vascular function as well as safety in patients with PBC.

Detailed Description
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Primary biliary cirrhosis (PBC) is often associated with abnormalities in serum lipids. Hypercholesterolemia is an established risk factor for cardiovascular morbidity and mortality. Since many PBC patients have a very slow progression of their underlying liver disease cardiovascular risk factors may become more relevant as prognostic facors. Whether statins lower serum cholesterol levels and reduce the cardiovascular risk in PBC patients remains to be determined. Statins are generally well tolerated and are not associated with an increased risk of hepatotoxicity in patients with nonalcoholic fatty liver disease (NAFLD). However only limited data on safety on statins in chronic cholestatic liver diseases are available. In a recent pilot study at the Medical University of Graz atorvastatin did not statistically increase liver enzymes in PBC patients. However, data on long-term treatment with atorvastatin in these patients are not yet available. Moreover, long-term treatment with statins may have potential beneficial immunomodulatory effects on the disease course of PBC in analogy to other immune-mediated disorders such as rheumatoid arthritis and multiple sclerosis.

Official Title
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Safety and Efficacy of Long-Term Treatment With Atorvastatin in Patients With Primary Biliary Cirrhosis

Conditions
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Primary Biliary Cirrhosis, Hypercholesterolemia

Intervention / Treatment
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* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LDL-cholesterol > 130 mg/dl Primary biliary cirrhosis (AMA positive or biopsy proven) Male or female gender Age 18-70 years Normal kidney function Exclusion Criteria: Primary biliary cirrhosis Stage III-IV (Ludwig Score) Liver cirrhosis Decompensated liver disease ( > Child-Pugh class B, ascites, esophageal varices) ALT or AST > 2x ULN Pregnancy or breastfeeding Premenopausal women without certain contraception Known hypersensitivity to HMG-CoA reductase inhibitors Current treatment with lipid-lowering agents other than atorvastatin; immunosuppressants, macrolides

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>Atorvastatin 10 mg per day for 48 weeks | Drug: Atorvastatin<br>* oral, 10 mg, daily, 48 weeks<br>* Other names: Sortis10 mg, 1-21927, C10AA05;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Low-density lipoprotein cholesterol (LDL-C) |  | week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intima-media thickness of the common carotid artery (IMT), vascular wall stiffness (stiffness index SI), flow-mediated dilation of the brachial artery (FMD) |  | week 0, 48 | 
| Total cholesterol, triglycerides, VLDL-C, HDL-C, lipid profile, hs-CRP, AP, GGT, bilirubin, bile acids, immunoglobins |  | week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60 | 
| AST, ALT, CK, PZ, AT, albumin, creatinine, blood cell count |  | week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholestasis, Atherosclerosis, Statins, Vascular function