Nonalcoholic fatty liver disease affects millions of people in the United States. The condition is often not detected until it is well advanced, and a definitive diagnosis requires an invasive biopsy of the liver. One subtype can lead to severe liver cirrhosis and cancer. Now, promising results from a preliminary study set the stage for a noninvasive test that only requires a stool sample. The test examines the makeup of gut microbes in the stool sample.

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Research has shown that the analysis of a stool sample could be enough to diagnose NAFLD.

The study – by researchers from the University of California-San Diego (UCSD) and colleagues from Human Longevity, Inc. in San Diego and the J. Craig Venter Institute in La Jolla, both in California – is published in the journal Cell Metabolism.

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by a buildup of fat in the liver. According to the National Institute of Diabetes and Digestive and Kidney Diseases, it is “one of the most common causes of liver disease in the U.S.”

NAFLD is a different condition to alcoholic liver disease, in which the fat buildup is due to heavy alcohol use.

In the new study – which involved 135 participants and establishes “proof of concept” – the researchers found that the stool-based test was able to predict advanced NAFLD with an accuracy of between 88 and 94 percent.

First author Rohit Loomba, a professor of medicine and director of the NAFLD Research Center at UCSD, says that determining who has or is at risk for NAFLD is a “critical unmet medical need.”

Although there are dozens of new drugs in the pipeline, if it were possible to better diagnose the disease, then patients could be better selected for trials and “ultimately [we] will be better equipped to prevent and treat it,” Prof. Loomba adds.

There are two forms of NAFLD: simple fatty liver and nonalcoholic steatohepatitis (NASH).

Fast facts about NAFLD
  • People with NAFLD often experience no symptoms.
  • Sometimes, people with one type of NAFLD are later diagnosed with the other type.
  • Having NAFLD raises the chance of developing cardiovascular disease.

Learn more about NAFLD

Simple fatty liver is a form of NAFLD in which there is fat in the liver but without inflammation or cell damage. This form does not usually lead to liver damage or complications.

NASH is type of NAFLD where, in addition to fat buildup, the liver also shows signs of inflammation and liver cell damage.

The inflammation can lead to scarring or fibrosis, and then to more severe cirrhosis, which alters the liver’s fundamental biology. NASH can also progress to liver cancer.

Nobody knows exactly what causes NAFLD, or why some of the people affected have simple fatty liver while others have NASH.

Estimates suggest that around 20 percent of people with NAFLD have NASH. In the U.S., between 30 and 40 percent of adults are thought to have NAFLD, and approximately 3 to 12 percent have NASH.

Being obese – and having conditions related to obesity, such as type 2 diabetes – raises the risk of developing NAFLD.

Prof. Loomba and colleagues note that NAFLD is thought to affect up to 50 percent of obese people.

In their study report, the researchers note how studies have shown that the makeup of a person’s gut microbiome – the trillions of microbes that live in the gut together with their genetic material – may affect their risk for obesity.

This set them wondering if there might also be a link between obesity-related liver disease and the gut microbiome. If this is true, then it may be possible to analyze the makeup of the gut microbiome from a person’s stool sample and link that to their NAFLD status.

To test this theory, the team first examined 86 patients with NAFLD diagnosed by biopsy – including 72 with mild or moderate disease and 14 with advanced disease.

They sequenced the genes from the participants’ stool samples – analyzing the presence, location, and relative abundance of various microbe species.

This process identified 37 species of bacteria that differentiated advanced NAFLD from the mild or moderate stage with 93.6 percent accuracy.

The researchers then validated the finding in a second group of 16 patients with advanced NAFLD and 33 healthy volunteers who acted as controls.

This time, they found that by testing the relative abundance of nine species of bacteria – seven of which were in the 37 identified previously – they could differentiate the NAFLD patients from the controls with 88 percent accuracy.

We believe our study sets the stage for a potential stool-based test to detect advanced liver fibrosis based simply on microbial patterns, or at least help us minimize the number of patients who have to undergo liver biopsies.”

Senior author Dr. Karen E. Nelson, president of the J. Craig Venter Institute

The researchers are keen to point out that so far, the test has only been trialed on a small number of patients in a highly specialized setting. Even if further studies validate it, a stool sample test for NAFLD is unlikely to be available for clinical use for at least 5 years.

Learn how a protein discovery may offer a new treatment target for NAFLD.