Mycophenolate Mofetil Versus Cyclosporin A in the Treatment of Primary Biliary Cholangitis-autoimmune Hepatitis Overlap Syndrome Due to Nonresponse to Standard Therapy

Study Overview
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Brief Summary
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Biochemical response of primary biliary cholangitis-autoimmune hepatitis overlap syndrome induced by mycophenolate mofetil versus cyclosporin A

Official Title
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Mycophenolate Mofetil Versus Cyclosporin A in the Treatment of Primary Biliary Cholangitis-autoimmune Hepatitis Overlap Syndrome Duo to Nonresponse to Standard Therapy

Conditions
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Hepatitis, Autoimmune, Primary Biliary Cholangitis, Immunosuppression

Intervention / Treatment
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* Drug: Cyclosporin A
* Drug: Mycophenolate Mofetil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18-70 years; Diagnosed with PBC-AIH overlap syndrome according to Paris criteria; Patients have a nonresponse to azathioprine; The WBC count ≥2.5x10^9/L and platelet count ≥50x10^9/L. Agreed to participate in the trial, and assigned informed consent; Exclusion Criteria: The presence of hepatitis A, B, C, D, or E virus infection; Patients with presence of serious decompensated cirrhosis; Patients have a history of glucocorticoid or immunosuppressant medication before enrollment; Liver damage caused by other reasons: such as primary sclerosing cholangitis, non-alcoholic steatohepatitis, drug induced liver disease or Wilson's disease. Pregnant and breeding women and women of childbearing age in need of reproduction Severe disorders of other vital organs, such as severe heart failure, cancer; Patients with presence of renal insufficiency; Parenteral administration of blood or blood products within 6 months before screening; Recent treatment with drugs having known liver toxicity; Taken part in other clinic trials within 6 months before enrollment. Patients who are allergic to these drugs; Uncontrolled infection and hypertension ;

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporin A<br> | Drug: Cyclosporin A<br>* Ursodeoxycholic acid combination of immunosuppressive agents(methylprednisolone with cyclosporin A)<br>|
| Active Comparator: Mycophenolate Mofetil<br> | Drug: Mycophenolate Mofetil<br>* Ursodeoxycholic acid combination of immunosuppressive agents(methylprednisolone with mycophenolate mofetil )<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical remission | The percentage of patients in biochemical remission, defined as normalization of serum ALT and IgG levels after 24 weeks of treatment, per treatment group. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial remission | Partial remission, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) serum levels >1x Upper Limit of Normal (ULN) and <2x ULN | up to 6 months | 
| Minimal response | Minimal response, defined as decrease of ALT or AST serum levels but still >2x ULN | up to 6 months | 
| Treatment failure | defined as no improvement or increase of ALT or AST serum levels | up to 6 months | 
| Changes in liver stiffness | liver stiffness will be measured by shear-wave elastography | up to 6 months | 
| Side-effects | Drug related side-effects | up to 6 months |