Diagnostic Techniques for Fatty Liver Disease

Overseen By Jessica L Olson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Excess alcohol, Pregnancy, MRI contraindications

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH) in the community. It aims to assemble a patient group to improve diagnostic techniques and understand long-term effects. Participants will undergo tests such as Magnetic Resonance Elastography (a special MRI that checks liver stiffness) and possibly a liver biopsy (a procedure to remove a small sample of liver tissue for examination). The trial seeks adults in Olmsted County who have not been diagnosed with NAFLD and are not heavy drinkers. As an unphased trial, it offers a unique opportunity to contribute to foundational research that could enhance future diagnostic methods.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that these diagnostic techniques are safe for assessing fatty liver disease?

Research has shown that liver biopsies are generally safe when experienced professionals perform them. Some individuals might experience pain at the needle insertion site. Ultrasound guidance can enhance safety and allow for quick discharge, sometimes within an hour after the biopsy.

Studies have found that Magnetic Resonance Elastography (MRE) provides a safe and noninvasive method to measure liver stiffness, particularly for individuals with nonalcoholic fatty liver disease (NAFLD). MRE avoids the use of needles, making it well-tolerated by most people.

Overall, both liver biopsy and MRE are safe. MRE is less invasive, while liver biopsy carries minor risks that healthcare professionals manage effectively. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of Magnetic Resonance Elastography (MRE) for diagnosing fatty liver disease because it offers a non-invasive alternative to the traditional liver biopsy. Unlike liver biopsies, which require inserting a needle into the liver and can be uncomfortable and risky, MRE is a type of MRI that can safely measure liver stiffness without any invasive procedures. This technique provides comprehensive imaging and data, helping doctors better understand and monitor the liver's condition. The potential for MRE to offer a safer and more comfortable diagnostic option is a significant advancement in managing and diagnosing fatty liver disease.

What evidence suggests that these diagnostic techniques are effective for assessing NAFLD?

Research has shown that liver biopsies can monitor the progression of Non-alcoholic Fatty Liver Disease (NAFLD) by taking direct samples from the liver. However, results may vary due to differences in the samples. In this trial, participants at risk for NAFLD will undergo Magnetic Resonance Elastography (MRE), a non-invasive method that accurately measures liver stiffness and diagnoses NAFLD. Studies indicate that MRE consistently measures liver stiffness in various situations, making it a useful tool for checking and monitoring liver health in people at risk for NAFLD. ^{2 4 6 7 8}

Who Is on the Research Team?

ALINA M ALLEN, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This study is for adults over 18 living in Olmsted County without a previous NAFLD diagnosis. It's not for those with MRI-incompatible devices, severe claustrophobia, heavy alcohol users (over 20g/week for women and 30g/week for men), or pregnant individuals.

Inclusion Criteria

I have never been diagnosed with fatty liver disease.

Olmsted County residents at the time of search

Exclusion Criteria

Currently pregnant

Alcohol in excess (more than 20 gm per week in women and 30 gm per week in men)

Have contraindications to MRI (MRI incompatible implanted devices, severe claustrophobia)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Assessment

Participants undergo Magnetic Resonance Imaging (MRE), blood tests, and possible biopsy to assess NAFLD and NASH

5 years

Follow-up

Participants are monitored for long-term health outcomes including the development of NAFLD, NASH, and related complications

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Liver biopsy
• Magnetic Resonance Elastography

Trial Overview The TONES study is looking at how common NAFLD and NASH are among people. It uses Magnetic Resonance Elastography, blood tests, Fibro Scan, and liver biopsies to build a detailed picture of these liver conditions.

How Is the Trial Designed?

Group I: Subjects at risk for NAFLD Experimental Treatment 4 Interventions

Adult Olmsted County residents identified as at risk for NAFLD will receive Magnetic Resonance Imaging (MRE,) blood tests,and possible biopsy.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Magnetic resonance elastography (MRE) is an effective and non-invasive method for detecting and staging liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), showing a high accuracy with an area under the ROC curve (AUROC) of 0.90 for advanced fibrosis (≥ F3).

MRE outperforms transient elastography (TE) and non-invasive scores (APRI and FIB-4) in accuracy, and while factors like liver inflammation can affect MRE results, only gamma-glutamyl transferase (GGT) was significantly associated with overestimation of liver stiffness in the analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver stiffness accuracy by magnetic resonance elastography in histologically proven non-alcoholic fatty liver disease patients: a Spanish cohort. Lara Romero, C., Liang, JX., Fernández Lizaranzazu, I., et al.[2023]

Magnetic resonance elastography (MRE) showed the highest diagnostic accuracy for detecting stage 4 liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) among the three tested methods, which included vibration-controlled transient elastography (VCTE) and two-dimensional shear wave elastography (2D-SWE).

MRE also demonstrated superior intra- and inter-observer reproducibility compared to VCTE and 2D-SWE, indicating that it provides more consistent results when assessing liver fibrosis stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct Comparison of US and MR Elastography for Staging Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease. Imajo, K., Honda, Y., Kobayashi, T., et al.[2022]

Sonography is the most commonly used method for diagnosing fatty liver diseases due to its availability and good diagnostic performance, although it has limitations in detecting mild steatosis and in obese patients.

Advanced techniques like the Controlled Attenuation Parameter (CAP) from FibroScan and MR-based methods such as MR spectroscopy and PDFF provide more precise quantification of liver fat and can serve as reference standards for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic methods of fatty liver diseases. Dvořák, K.[2022]

MR elastography (MRE) is a promising non-invasive technique for assessing liver fibrosis, but it still requires further validation before it can be widely adopted in clinical practice.

In a study involving 104 patients, MRE was compared to transient elastography for diagnosing fibrosis in nonalcoholic fatty liver disease, highlighting the need for critical evaluation of its effectiveness against established methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRE in NAFLD: Promising but Further Validation is Required. Ryan, JD., Tsochatzis, EA.[2021]

3D magnetic resonance elastography (3D-MRE) shows superior diagnostic accuracy for advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) compared to 2D-MRE, with an area under the receiver operator curve (AUROC) of 0.981 versus 0.921.

MRE techniques, despite some limitations, are valuable for non-invasive assessment and risk stratification of liver fibrosis in NAFLD patients, using liver biopsy as the reference standard.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Editorial: Magnetic Resonance Elastography and Non-Alcoholic Fatty Liver Disease: Time for an Upgrade? Flores, A., Asrani, SK.[2018]

In a study of 104 adults with nonalcoholic fatty liver disease (NAFLD), magnetic resonance elastography (MRE) was found to be significantly more accurate than transient elastography (TE) for diagnosing liver fibrosis, with an area under the receiver operating characteristic curve (AUROC) of 0.82 compared to TE's 0.67.

MRI-based proton density fat fraction (MRI-PDFF) analysis demonstrated exceptional accuracy in detecting steatosis, achieving an AUROC of 0.99, which was superior to the controlled attenuation parameter (CAP) method, which had an AUROC of 0.85.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Elastography vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease. Park, CC., Nguyen, P., Hernandez, C., et al.[2022]

In a study of 111 patients with severe to morbid obesity, MR elastography demonstrated a higher examination success rate (95.8%) compared to VCTE (81.3% to 88.5%), indicating it is more reliable for assessing liver stiffness.

Both MR elastography and VCTE showed excellent diagnostic accuracy for detecting significant hepatic fibrosis, with MR elastography also exhibiting better interobserver agreement than liver biopsy, making it a promising tool for liver assessment in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Performance of MR Elastography and Vibration-controlled Transient Elastography in the Detection of Hepatic Fibrosis in Patients with Severe to Morbid Obesity. Chen, J., Yin, M., Talwalkar, JA., et al.[2022]

In a study of 119 adults with nonalcoholic fatty liver disease, there was a significant 43.7% discordance rate between magnetic resonance elastography (MRE) and transient elastography (TE) in determining liver fibrosis stages, indicating that these two methods do not always agree on fibrosis assessment.

Body mass index (BMI) was found to significantly influence the discordance between MRE and TE results, with higher BMI associated with increased discrepancies in fibrosis staging, suggesting that obesity may affect the accuracy of these noninvasive liver assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients With Nonalcoholic Liver Disease. Caussy, C., Chen, J., Alquiraish, MH., et al.[2020]

Magnetic resonance elastography (MR elastography) demonstrated high diagnostic accuracy (AUROC = 0.93) for detecting nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD), with a sensitivity of 94% and specificity of 73%.

The study found that hepatic stiffness measurements can differentiate between patients with simple steatosis, those with inflammation but no fibrosis, and those with fibrosis, indicating that MR elastography can identify NASH even before fibrosis develops.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Chen, J., Talwalkar, JA., Yin, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37604268/

Progression of non-alcoholic fatty liver disease and long-term ... Over a median of 3.4 years between biopsies, 30.4% (218/718) experienced NAFLD progression, including 12.5% (62/497) with incident non-fibrotic ...

2. americanjir.com americanjir.com/safety-of-1-h-discharge-after-percutaneous-liver-biopsy-a-systematic-review-and-meta-anal-ysis/

Safety of 1-h discharge after percutaneous liver biopsy One-hour discharge following a percutaneous liver biopsy is safe, particularly when performed under ultrasound guidance and with selective ...

3. gastrojournal.org gastrojournal.org/article/S0016-5085(05)00630-X/fulltext

Sampling Variability of Liver Biopsy in Nonalcoholic Fatty ... In conclusion, this study demonstrates significant sampling variability of routine liver biopsy in patients with NAFLD. This can result in diagnostic and ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168827823050638

Progression of non-alcoholic fatty liver disease and long ... Over a median of 3.4 years between biopsies, 30.4% (218/718) experienced NAFLD progression, including 12.5% (62/497) with incident non-fibrotic NASH, 24.0% (141 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2211568413002684

Transjugular liver biopsy: Indications, technique and results Transjugular liver biopsy is a safe, effective and well-tolerated technique to obtain liver tissue specimens in patients with diffuse liver disease.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK553146/

Percutaneous Liver Biopsy - StatPearls - NCBI Bookshelf - NIH Percutaneous liver biopsy provides a method for accurate histological evaluation of a wide range of liver pathologies. It continues to play a ...

7. mayoclinic.org mayoclinic.org/tests-procedures/liver-biopsy/about/pac-20394576

Liver biopsy A liver biopsy is a safe procedure when done by an experienced healthcare professional. Possible risks include: Pain. Pain at the biopsy site is ...

8. scientificarchives.com scientificarchives.com/article/endoscopic-ultrasound-guided-liver-biopsy-the-pathologists-perspective

Endoscopic Ultrasound-Guided Liver Biopsy EUS-LB was found to be safe and associated with less pain, shorter hospital stay, and high diagnostic yield (93%) compared to PC-LB.