Liver Fibrosis in Sickle Cell Disease

Completed

• Conditions: Sickle Cell Disease
• Interventions: Other: Liver transient elastography (Fibroscan); Other: Ferriscan; Procedure: Liver biopsy in iron overloaded subjects.

• Registration Number: NCT02007746
• Lead Sponsor: University of Miami

Brief Summary

Patients with sickle cell disease many have a number of systemic complications, including liver problems. Some of these liver problems lead to liver fibrosis/cirrhosis, secondary to chronic blood transfusions. The purpose of this study is to investigate FibroScan readings in patients with sickle cell disease and iron overload secondary to blood transfusions, and to correlate the FibroScan results with Ferriscan. A comparison with the results of FibroScan to patients with Sickle cell without known liver disease, who have never been on chronic transfusions and with normal liver function profiles will also be made.The primary hypothesis is that the results of FibroScan will correlate with the results of Ferriscan and liver biopsy.

Detailed Description

Liver biopsy is the gold standard to examine the liver for iron deposits and histology. However, liver biopsy is invasive and involves a risk of bleeding and pain. Biopsy may also miss significant pathology if the small biopsy specimen is taken from an uninvolved part of the liver. Non-invasive techniques such as MRI are now used to evaluate the liver iron content. MRI can visualize the whole liver and measure liver iron content. MRI, however, will not detect liver scarring.

Liver transient elastography (FibroScan) is a non-invasive ultrasound tool for assessing liver fibrosis or scarring by measuring liver stiffness (LSM). Compared with liver biopsy, FibroScan provides immediate results and is a painless, short (3 mins), simple procedure to perform. In some studies FibroScan reports have correlated well with liver biopsy results of fibrosis and cirrhosis, and with Ferriscan, ferritin and liver function tests.

This purpose of this study is to investigate the role of FibroScan in individuals with sickle cell anemia and iron overload or who have a diagnosis of liver disease, and to compare FibroScan readings with magnetic resonance imaging.

We will also compare the results of the Fibroscan with liver biopsy.

This study will also compare the results of FibroScan to patients with Sickle cell without any known liver disease, who have never been on chronic transfusions (defined as no more than 4 transfusions in lifetime) and who have normal liver function profiles.

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2013-12-06
• Study First Submitted QC: 2013-12-06
• Study First Posted: 2013-12-11
• Primary Completion: 2017-06-01
• Study Completion: 2017-06-01
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-21
• Last Update Posted: 2021-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• pediatric patients age 10 years and older with sickle cell disease

• meeting other criteria:

  1. history of chronic transfusion and iron overload and/or
  2. known liver disease related to sickle cell or iron overload

• signed consent and assent (as applicable)

Exclusion Criteria

• children younger than 10 years
• Pregnant females
• Prisoners
• Other causes of liver disease, unrelated to sickle cell or iron overload

Inclusion criteria for controls:

• Patients 10 years and older with sickle cell disease without history of chronic transfusions (less than 4 transfusions in a lifetime)
• and without obvious liver disease.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subjects with sickle cell disease and iron overload	Liver transient elastography (Fibroscan)	Patients will have blood tests done to evaluate liver function and general health, then have FibroScan and Ferriscan. A blinded (no access to laboratory parameters or available data) radiologist will interpret the Ferriscan. Liver biopsy will be also obtained (if not done within the previous year). Otherwise, the results of the recent liver biopsy will be collected.
Subjects with sickle cell disease and iron overload	Liver biopsy in iron overloaded subjects.	Patients will have blood tests done to evaluate liver function and general health, then have FibroScan and Ferriscan. A blinded (no access to laboratory parameters or available data) radiologist will interpret the Ferriscan. Liver biopsy will be also obtained (if not done within the previous year). Otherwise, the results of the recent liver biopsy will be collected.
control patients with sickle cell disease	Liver transient elastography (Fibroscan)	Patients 10 years and older with sickle cell disease without history of chronic transfusions (less than 4 transfusions in a lifetime) and without obvious liver disease. Will have liver function blood tests and general health check ups. Then will have FibroScan performed. No liver biopsy will be performed in control patients.
Subjects with sickle cell disease and iron overload	Ferriscan	Patients will have blood tests done to evaluate liver function and general health, then have FibroScan and Ferriscan. A blinded (no access to laboratory parameters or available data) radiologist will interpret the Ferriscan. Liver biopsy will be also obtained (if not done within the previous year). Otherwise, the results of the recent liver biopsy will be collected.

Primary Outcome Measures

Name	Time	Method
Liver transient elastography (FibroScan) of liver iron content and stiffness	at imaging visit (3 minutes)	Liver transient elastography (FibroScan) uses a probe consisting of an ultrasound transducer located at the end of a vibrating piston. The piston produces a vibration of low amplitude and frequency, which generate a shear wave that passes through the skin and liver tissue. The ultrasound then detects the propagation of the shear wave through the liver (at a depth of 25 - 65 mm below the skin surface) by measuring its velocity. The shear wave velocity is directly related to the tissue stiffness, with a higher velocity equating to higher tissue stiffness, corresponding to increasing severity of fibrosis.

Secondary Outcome Measures

Name	Time	Method
magnetic resonance imaging (MRI) measure of liver iron content and stiffness	at imaging visit (about 30-60 minutes)
liver function tests (ALT, AST, serum alkaline phosphate, GGTP, total bilirubin, direct bilirubin), complete blood count, platelets, reticulocyte count, serum ferritin to assess liver function and evaluate overall health	at clinic visit blood draw (about 1 minute)

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States