Noninvasive Stepwise Approach is Effective in Diagnosing Advanced Liver Fibrosis in NAFLD

Method can eliminate need for liver biopsies in significant number of patients

A noninvasive stepwise approach (SWA) to diagnose advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is more accurate than other measures and can reduce the number of liver biopsies needed, according to Cleveland Clinic research presented at the American College of Gastroenterology’s 2019 annual meeting.

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“The diagnostic accuracy of the SWA was approximately 70% — significantly better than NAFLD Fibrosis Score (NFS) or the Liver Stiffness Measurement (LSM) alone,” says gastroenterologist Arthur McCullough, MD, the study’s primary author. “In patients with an NFS score <-1.455, SWA obviated the need for a liver biopsy.”

Integrating two parameters into a single diagnostic model

Advanced liver fibrosis results in cirrhosis, liver failure and portal hypertension and often requires liver transplantation. Accurate diagnosis is essential for clinical intervention. The current gold standard is liver biopsy. Although as much as 20% of patients with NAFLD present with advanced fibrosis over the course of their lifetime, arriving at this diagnosis using non-invasive methods remains a challenge, Dr. McCullough explains.

“Let’s put things into perspective — out of approximately 80-100 million people with NAFLD in the United States, with a very conservative estimate [10% rate of liver fibrosis], approximately 10 million will have advanced fibrosis,” he says. “We can’t know who these people are without a liver biopsy, and we can’t do a liver biopsy for all of them. So we continuously investigate non-invasive ways to make a diagnosis.”

The recently proposed two-step noninvasive SWA model that Dr. McCullough and his colleagues evaluated consists of first classifying patients based on NFS, followed by classification based on the LSM as determined by FibroScan®. This ultrasound technology measures the velocity of sound waves transiting the liver and converts that value into a measurement of liver stiffness, an approach known as liver ultrasonographic elastography.

“We chose NFS because one of the components of that score is the presence or absence of diabetes, and we know that diabetes is the single biggest risk factor for development of advanced fibrosis,” says Dr. McCullough. “FibroScan has the convenience of being used right in the doctor’s office, without the need for a separate radiology appointment.”

The SWA was first proposed by hepatologist Ariel E. Feldstein, MD, former Director of Research of Cleveland Clinic’s Pediatric Institute, who currently serves as Chief of Gastroenterology, Hepatology and Nutrition at the University of California, San Diego School of Medicine’s Rady Children’s Hospital. The model had not been tested in practice. The present single-center study aimed to assess the clinical value of SWA in reducing the number of liver biopsies in patients with NAFLD.

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“The major goal of our study was to test and verify that SWA would obviate the need for liver biopsy in a significant number of patients,” says Dr. McCullough.

Less risk and greater cost-effectiveness associated with SWA

Ninety-eight patients who had FibroScan and liver biopsy done less than six months apart in 2017 and 2018 were included in the study.

The NFS, LSM and Fibrosis (F) score on biopsy were determined for each patient. Patients were then separated into three groups based on their NFS scores: low risk (< -1.455), intermediate (-1.455-0.675) and high risk (>0.675). A FibroScan was performed on patients in each group. Liver biopsy was done only in those patients with an NFS >-1.455, LSM > 10kPA and/or a combination of both. The biopsy result was compared to the accuracy of using NFS alone, LSM alone or SWA to diagnose advanced fibrotic disease.

The researchers found that SWA had the highest diagnostic accuracy (90%), with a sensitivity of 73%, a specificity of 96%, a positive predictive value of 80% and a negative predictive value of 94%.

“Of the 98 patients in our study, 16 would not have needed a liver biopsy” based on SWA, says Dr. McCullough. “Furthermore, a lot of doctors in our group do biopsies even if the predictive NFS scores are low, which was the case for 18 patients in our study whose NFS and FibroScan scores were both low. Those patients would not have had to be biopsied based on SWA.”

 Low-risk patients with NFS < 1.455 did not significantly benefit from subsequent LSM to rule out advanced fibrosis, the researchers found. Results showed that patients with high-risk NFS and high-risk LSM could safely defer biopsies and be treated as compensated cirrhosis unless otherwise indicated.

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The SWA’s main advantages over other methods used to diagnose advanced liver fibrosis include its non-invasive nature and the resulting smaller risk to the patient, and its greater cost effectiveness.

“We have so many patients with fatty liver disease and doing a lot of liver biopsies would be very expensive,” says Dr. McCullough. “In addition, a lot of patients do not want to undergo a liver biopsy due to the risks associated with the procedure.”

Integrating SWA into clinical practice

While the study’s findings are encouraging, Dr. McCullough says the SWA’s diagnostic accuracy should be confirmed in a larger group of patients, and at other medical centers, before its full clinical implementation. As a follow-up to this research, his group plans to investigate whether specific patient characteristics influence the SWA’s diagnostic accuracy.

“We have noticed that in patients who are very heavy [body mass index >30], the FibroScan is particularly inaccurate, so our next step would be to look at specific patient characteristics that would make the SWA more effective,” he says.