Development of a Novel Biomarker for Liver Fibrosis

NCT ID: NCT02348814

Last Updated: 2019-04-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 25 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2019-02-26

Brief Summary

The overall aim of this study is to validate a quantitative digital tool for staging liver fibrosis in biopsies from chronic human liver diseases and then evaluate it prospectively in patients.

Detailed Description

Preliminary data suggest that cholesterol and retinoid metabolism are tightly linked in these cells, prompting us to examine this relationship in the setting of obesity and diabetes. Specific aims have been developed to test the following hypotheses: 1) Quantifying liver fibrosis as a continuous variable will predict clinically significant outcomes in fatty liver disease related to metabolic syndrome; and 2) In a prospective cohort of patients, quantified liver fibrosis will correlate more strongly with tissue and circulating retinoid metabolites than with other, commonly measured serum markers.

This study offers a major innovation by performing accurate fibrosis quantification without any human intervention or post-analysis correction. In addition, we can test whether subtle differences in quantified fibrosis impact outcome for a given clinical stage of disease severity, possible because we are measuring fibrosis as a continuous variable, not a categorical one. We are using a disease-independent approach to evaluate anti-fibrotic agents in clinical trials and for evaluating other diagnostic markers.

We are also testing whether a novel diagnostic marker, retinoid storage, correlates with liver disease progression in humans. We propose to extend the study to address fatty liver disease, NAFLD/NASH, in the context of adult patients with abnormal liver tests, fatty liver identified on imaging, physical obesity, and diabetes. Clinical variables and outcomes to be recorded and analyzed include: morphology (age, gender, ethnicity, height, weight/BMI, waist circumference and steatosis on imaging studies); biochemistry (glucose intolerance or diabetes, complete blood counts, metabolic panels, liver function tests, cholesterol panels, insulin, and vitamin D levels); clinical outcomes (date of liver disease diagnosis and estimated duration of disease, listing on liver transplant list, occurrence of liver transplant or re-transplant, presence of cancer, and death); medications (current or previous prescribed, herbals, supplements taken for diabetes, dyslipidemia, hypertension, cardiovascular disease, or stroke); and disease exacerbation/modifying factors (presence of other chronic liver diseases such as NASH + HIV, liver toxins such as alcohol consumption, weight gain, or worsening diabetes).

Data will be collected from subjects who complete eight visits over a 24-month period. Assessments will include morphometric measurements, blood collection for laboratory analysis and completion of dietary history report.

Conditions

Liver Fibrosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

normal weight

BMI 20-25

No interventions assigned to this group

overweight

BMI 25-30

No interventions assigned to this group

obese

BMI 30-35

No interventions assigned to this group

morbidly obese

BMI \> 35

No interventions assigned to this group

non-diabetic

HgbA1c (\<5.7%) and blood glucose (65-99 mg/dL) within normal range as defined at UCLA Clinical Lab

No interventions assigned to this group

diabetic

HgbA1c (\>6.5%) and blood glucose (\>100 mg/dL) as defined at UCLA Clinical Lab

No interventions assigned to this group

non-cirrhotic

Normal liver function tests (AST/SGOT, ALT, SGPT, alkaline phosphatase, bilirubin) as defined at UCLA Clinical Lab

No interventions assigned to this group

dyslipidemic

Abnormal lipid profile (Total cholesterol \>170 mg/dL, LDL \>100 mg/dL, HDL \>130 mg/dL, triglycerides \>150 mg/dL) as defined at UCLA Clinical Lab

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Age >/= 18 years
• At least one liver function test abnormality (AST/SGOT, ALT/SOT, alkaline phosphatase, or bilirubin) defined as a value outside of the normal range at UCLA clinical labs. This must be present on at least two occasions within a 24 month consecutive period
• Any body mass index > 20
• One of the following:
• Clinical indication, according to standard of care assessment, for undergoing image-guided percutaneous (or transjugular) liver biopsy
• Eligible for weight loss (bariatric) surgery with fatty liver disease
• NAFLD/NASH patient who meets the above criteria and has already undergone a liver biopsy for diagnosis and disease staging
• NAFLD/NASH patient who meets above criteria but chooses not to participate in the liver biopsy, extra blood draws or the dietary assessment for the study.

Exclusion Criteria

• Age < 18 years
• Current pregnancy
• Significant clinical co-morbidities that would preclude getting either a percutaneous or transjugular liver biopsy (i.e. platelets < 50, 000 or International Normalized Ratio (INR) > 1.5 or Hemoglobin < 8)
• Unwilling or unable to participate or consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Simon Beaven

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Simon Beaven, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

UCLA Dept of Medicine, Division of Digestive Diseases

Locations

UCLA Clinical and Translational Research Center (CTRC)

Los Angeles, California, United States

Countries

United States

Other Identifiers

UL1TR000124

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1TR000124-2016

Identifier Type: -

Identifier Source: org_study_id