Early Identification of Myocardial Impairment in PBC (EARLY-MYO-PBC)

EARLY Identification of MYOcardial Impairment in Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is a chronic inflammatory liver disease leading to cirrhosis. Researches reported patients with PBC may involve abnormalities on skeleton, thyroid and exocrine glands. However, whether this autoimmune disease would cause cardiac impairment is scarcely investigated. Cardiovascular Magnetic Resonance(CMR) is recently developed as a reliable modality to evaluate the cardiac tissue characteristics and functions. This study aims to investigate the cardiac status in PBC patients based on CMR.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Abnormalities; Primary Biliary Cholangitis
• Intervention / Treatment: Diagnostic test: CMR examination

Detailed Description

Primary biliary cholangitis (PBC) is a progressive and uncommon inflammatory autoimmune cholesteric liver disease，which will contribute to cirrhosis. Symptoms and course of primary biliary cholangitis can be diverse, wherefore the targets of the current treatment are focused on the prevention of end-stage liver disease. Researches reported patients with PBC may involve abnormalities on skeleton, thyroid and exocrine glands. However, whether this autoimmune disease would cause cardiac impairment is scarcely investigated. From our clinical practice, the cardiac structural abnormal can be found in certain patients with PBC detected by cardiovascular magnet resonance (CMR). CMR is the primary and emerging imaging modality for myocardial tissue characterisation, and it is recommended as a gold standard for functional imaging and assessment. This single-center, prospective observational study plans to identify the type and the severity of cardiac changes in PBC.

• Study Type: Observational
• Enrollment (Actual): 112

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Renji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Consecutive subjects were prospectively enrolled into 2 cohorts between September 2017 and December 2018. The cohorts were divided as follows: the PBC patients group and the control group.

Description

Inclusion Criteria for PBC group:

• Age between 18-80 years old.

• Definite primary biliary cirrhosis diagnosis which is consistent with European Association for the Study of the Liver (EASL) [Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis (2017)]. The following three diagnostic factors, at least meet two:

  1. History of elevated alkaline phosphatase (ALP) levels;
  2. Liver biopsy consistent with PBC;
  3. Positive antimitochondrial antibodies (AMA) or specific antinuclear antibodies.
• Providing written informed consent

Exclusion Criteria:

• History or presence of other concomitant liver disease including:

  1. Viral hepatitis;
  2. Inherited metabolic liver disease;
  3. Drug-induced liver injury;
  4. Other systemic disease inducing liver change.
• Subjects with known ischemic/non-ischemic cardiomyopathy.
• Subjects with standard metallic contraindications to CMR (i.e., estimated glomerular filtration rate < 30 ml/min/1.73 m2, New York Heart Association functional capacity class IV)

Inclusion Criteria for Control group:

• Absence of known systemic diseases
• Normal examinations in CMR/Echo/ECG
• Age between 18-80 years old.
• Providing written informed consent

Exclusion Criteria:

• Subjects with known heart disease including:

  1. Documented coronary artery disease;
  2. Ischemia/non-ischemia cardiomyopathy;
  3. Other systemic disease inducing heart change.

• Subjects with known liver disease including:

  1. Viral hepatitis;
  2. Inherited metabolic liver disease;
  3. Drug-induced liver injury;
  4. Other systemic disease inducing liver change.
• Subjects with standard metallic contraindications to CMR

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PBC group; Patients have a definite PBC diagnosis.	Diagnostic test: CMR examination; After recruiting participants and collecting the baseline information, a CMR scan and a post-processed imaging procedure will be carried on in order to detect the cardiac impairment.
Control group; The healthy volunteers or patients in Renji Hospital whose medical examinations show no systemic disease, and the CMR examinations are normal.	Diagnostic test: CMR examination; After recruiting participants and collecting the baseline information, a CMR scan and a post-processed imaging procedure will be carried on in order to detect the cardiac impairment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of cardiac involvement	Assessments base on the cardiac structure, function and tissue characterization	through study completion, an average of 14 months
Composite endpoint of quantitative assessment in cardiac injury	Compose of extracellular volume(%), T1 value(ms) and T2 value(ms).	within 2 days of CMR scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite endpoint of liver condition	Compose of the alanine aminotransferase (ALT), Aspartate aminotransferase (AST) ,alkaline phosphatase (AKP) and bilirubin indicating the liver condition and prognosis.	within 2 days of CMR scan
Composite endpoint of cardiac function	Compose of CRP (hs-CRP), troponin I (TnI) and hematocrit indicating the cardiac function	within 2 days of CMR scan

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Chair: Xiong Ma, MD,PhD, RenJi Hospital, School of Medicine, Shanghai Jiantong University

Publications and helpful links

General Publications

• Jiang P, Feng Z, Sheng L, Hu C, Ma X, Zhang S, Wu L, Xiao X, Wang Q, Guo C, Qiu D, Fang J, Xu J, Gershwin ME, Jiang M, Ma X, Pu J. Morphological, Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis. Clin Gastroenterol Hepatol. 2022 May;20(5):1112-1121.e4. doi: 10.1016/j.cgh.2021.08.035. Epub 2021 Aug 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2017
• Primary Completion (ACTUAL): February 1, 2019
• Study Completion (ACTUAL): April 3, 2019

Study Registration Dates

• First Submitted: February 1, 2018
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (ACTUAL): June 4, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 31, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Cardiovascular Magnetic Resonance; Primary Biliary Cholangitis; Cardiac impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Congenital Abnormalities; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cardiovascular Abnormalities; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: 201709P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No