NASH: Non-invasive Diagnostic Markers and Imaging

Summary

Rationale:

Non-alcoholic fatty liver disease (NAFLD) is the most widespread liver disorder in Western society (prevalence 20-30%). It is strongly associated with overweight and obesity. The majority of patients have simple steatosis. However, in about 15-30% of the subjects, a chronic inflammatory state develops that is referred to as non-alcoholic steatohepatitis (NASH), which leads to an overall increase in morbidity and mortality due to the progression to fibrosis, cirrhosis and in some cases, hepatocellular carcinoma (HCC). The term NAFLD comprises both simple steatosis and NASH. Most patients with NAFLD have no or few, mainly aspecific symptoms; and generally there is a silent progression of simple steatosis to NASH and in the end, liver-related morbidity and mortality.

To date, liver biopsy is the most sensitive test for detecting and staging NAFLD, and is the only reliable method for differentiating between NASH and simple steatosis. However, the procedure of obtaining a liver biopsy is invasive and associated with patient discomfort, significant complications and high costs. In addition, liver biopsy is prone to sampling error and inter- and intra-observer variability, due to the small size of liver biopsy samples. This method is therefore not suitable for screening large numbers of subjects at risk, or for follow-up of patients with NASH over time. Hence, only subjects at high risk (usually based upon elevated aminotransferase levels, which is not specific for the presence of NASH) are biopsied, leading to an underestimation of NASH prevalence and undertreatment. Further insight into disease mechanisms and risk factors for NAFLD and in particular NASH is warranted, to enable early diagnosis, adequate therapy and preventive measures to improve health status of these individuals. Accurate and less invasive methods to evaluate NASH, and NAFLD, are urgently needed.

Objective: The primary objective of this study is to establish non-invasive tools (e.g. biomarkers and imaging) to accurately diagnose patients with NASH. The secondary objective is to show an association between the levels of identified markers and disease severity.

Study design:

Eligible subjects will be included via the outpatient clinics Zuyderland in Heerlen, the Catharina hospital in Eindhoven and MUMC+ in Maastricht. A subset of eligible subjects has undergone a liver biopsy for clinical reasons. It is estimated that about 85% of subjects will be asked to undergo a biopsy for study purposes only. Liver biopsies for study purposes will be performed during a surgical procedure, e.g. bariatric surgery or cholecystectomy.

Blood, faeces and exhaled air will be collected and a FibroScan (+CAP) will be performed during a study visit. An MRI will be performed, to estimate the degree of steatosis. Furthermore, anthropometric data (weight, height, abdominal and waist circumference and blood pressure (BP)) will be collected.

The participants in the group undergoing liver biopsy during bariatric surgery will be asked permission to be approached for follow-up measurements 3 months post-surgery. As they will lose weight, which is associated with improvement of hepatic steatosis, this enables assessment of possible changes over time. A routine follow-up visit post-surgery will take place after 3 months. The follow-up measurements will be combined with this visit, minimizing the burden for the participant. The measurements will consist of blood, faeces and exhaled air collection and a FibroScan (+CAP) will be performed during a study visit. Furthermore, weight, height, BP and abdominal and waist circumference will be measured.

Study population:

Subjects with proven NAFLD by histology or NAFLD proven by imaging, who are undergoing surgery (i.e. bariatric surgery or cholecystectomy) will be asked to participate in this study. Furthermore, all subjects have to be between 18 and 65 years old.

Main study parameters/endpoints:

Non-invasive tool based on biomarkers and imaging to diagnose NASH.

Conditions

• Nonalcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Sponsors & Collaborators

• Zuyderland Medical Centre

  collaborator OTHER

• Maastricht University Medical Center

  lead OTHER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-04-30

Primary Completion

2017-10-31

Completion

2017-12-31