Clinical trial NCT01985009: Prospective, Cross-sectional and Multicenter Study, Evaluating the Diagnosis Accuracy of the Controlled Attenuation Parameter(CAP) Measured by FibroScan® (Either With M+ or XL+ Probe) in Patient With Non-Alcoholic Fatty Liver Disease Using Liver Biopsy as Reference.
Official title: Evaluating the Diagnosis Accuracy of the Controlled Attenuation Parameter(CAP) Measured by FibroScan® (Either With M+ or XL+ Probe) in Patient With Non-Alcoholic Fatty Liver Disease (NAFLD)Using Liver Biopsy as Reference.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Lead sponsor: Echosens
Sponsor class: INDUSTRY
First posted: 2013-11-15
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The non-alcoholic fatty liver disease (NAFLD) represents the most common cause of liver disease in the western world. It can progress from steatosis to non-alcoholic steatohepatitis (NASH), and then onto cirrhosis where there is a concomitant risk of developing hepatocellular carcinoma (HCC). The prevalence of hepatic steatosis is high, ranging from 16 to 31% in the general population, up to 80% in the obese populationand up to 96% in severely obese patients.

Liver biopsy (LB) has traditionally been regarded as the gold standard for the assessment of patients with NAFLD, although it has several limitations. LB has a potential sampling error, is an invasive and often painful procedure.

The natural history of patients with NAFLD is generally determined by the extent of liver fibrosis, hence non-invasive assessment of fibrosis with FibroScan® is often sufficient. For patients with proven NASH, changes in hepatic steatosis and serum ALT levels may provide information on the patient's course and/or response to treatment.

Several clinical studies have shown the benefit of measuring hepatic stiffness with the FibroScan® machine using the M+ probe. The ability to identify significant fibrosis and cirrhosis has been demonstrated in normal and overweight patients affected with chronic hepatitis B and C, biliary diseases, alcohol related liver disease (ALD) and NAFLD.

Recently, Echosens has also developed a novel ultrasonic controlled attenuation parameter (CAP) designed to quantify hepatic steatosis using a process based on vibration controlled transient elastography (VCTE™). Studies comparing CAP with liver biopsies in multi-aetiology cases and patients with Hepatitis C Virus (HCV) have shown that there is a good correlation between steatosis assessed histologically and using CAP.

The main objective of this prospective study is to evaluate the diagnosis accuracy of the Controlled attenuation Parameter (CAP) measured by FibroScan® (either with M+ or XL+)in patients with NAFLD to assess liver steatosis using biopsy as a reference.

The study involves adults' patients with suspected NAFLD scheduled to have a liver biopsy within 2 weeks of fibroscan examination and followed by the Hepatology service of four centers in United Kingdom.

Approximately 450 patients (of which 350 will be evaluable) will be enrolled in this study: Around 100 patients will be measured with the M+ probe and around 250 with the XL+ probe.

The inclusion period is from 18 to 24 months. Starting date: January 2014. End of recruitment: June 2017. The duration of the study for a patient is from 1 to 7 days, depending to the exams calendar.


Eligibility criteria: Inclusion Criteria:

* Patients must be at least 18 years of age
* Patients must be able to give written informed consent
* Patients with suspected NAFLD
* Patients scheduled to have a liver biopsy within 2 weeks of Fibroscan examination
* HBsAg negative, Anti-HCV negative, HCV-RNA negative, HBV-DNA negative

Exclusion Criteria:

* Unable or unwilling to provide written informed consent
* Patients with ascites
* Pregnant women
* Patients with any active implantable medical device (such as pacemaker or defibrillator)
* Patients who have had a liver transplant
* Patients with cardiac failure and/or significant valvular disease
* Patients with hematochromatosis
* Refusal to undergo a liver biopsy and/or blood test
* Alcohol consumption above recommended limits (\>14 units/week for women and \>21 units/week for men)
* Confirmed diagnosis of active malignancy, or other terminal disease
* Patient participation in another clinical trial within the preceding 30 days

Primary outcomes:
measure: Performance of CAP will be assessed using ROC analysis for the detection of steatosis above 5% - 10% - 30% and 60% using liver biopsy as the reference.
timeFrame: Up to 24 month
Secondary outcomes:
measure: Clinical, histological and biological factors associated CAP will be assessed using multivariate correlation.
timeFrame: Up to 24 month
Other outcomes:
measure: Performances of stiffness will be assessed by ROC analysis for the diagnosing above or equal to F2 fibrosis and cirrhosis (F4)using liver biopsy as the reference.
timeFrame: Up to 24 month
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre Nottingham
city: Oxford
country: United Kingdom
facility: John Radcliffe Hopsital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
References:
citation: Newsome PN, Sasso M, Deeks JJ, Paredes A, Boursier J, Chan WK, Yilmaz Y, Czernichow S, Zheng MH, Wong VW, Allison M, Tsochatzis E, Anstee QM, Sheridan DA, Eddowes PJ, Guha IN, Cobbold JF, Paradis V, Bedossa P, Miette V, Fournier-Poizat C, Sandrin L, Harrison SA. FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study. Lancet Gastroenterol Hepatol. 2020 Apr;5(4):362-373. doi: 10.1016/S2468-1253(19)30383-8. Epub 2020 Feb 3.
citation: Eddowes PJ, Sasso M, Allison M, Tsochatzis E, Anstee QM, Sheridan D, Guha IN, Cobbold JF, Deeks JJ, Paradis V, Bedossa P, Newsome PN. Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2019 May;156(6):1717-1730. doi: 10.1053/j.gastro.2019.01.042. Epub 2019 Jan 25.