Cancer; Digestive; Discovery

Taking aim at fatty liver, cancer with new blood test

Cancer; Digestive; Discovery

diseased liver
Nonalcoholic fatty liver disease is the leading cause of liver cancer. UT Southwestern has developed a blood test to identify patients at high risk and show how well treatment is working.

A novel blood test developed at UT Southwestern could inform how doctors treat nonalcoholic fatty liver disease (NAFLD) and reduce the risk of associated liver cancer.

The blood test identifies a biomarker – a serum protein measurement – that can tell us not only which patients with NAFLD are most at risk for liver cancer but also how well their treatment is working.

NAFLD, which affects roughly one-fourth of U.S. adults, is an emerging public health problem that dovetails with the country’s twin epidemics of obesity and type 2 diabetes. An estimated 30-40% of adults have an accumulation of fat in their liver, which causes inflammation and can lead to scarring (cirrhosis) and cellular damage.

People with NAFLD have up to a 17 times increased risk of developing liver cancer. Between 2009 and 2019, liver cancer deaths associated with NAFLD increased an average of 2.47% each year. Texas has a higher rate of liver cancer than the rest of the U.S. – 10.5% vs. 7.6%. And it’s rising every year.

Yujin Hoshida, M.D., Ph.D
Yujin Hoshida, M.D., Ph.D

NAFLD often progresses silently, and patients do not notice symptoms such as weight loss, swelling, or jaundice (yellowed skin) until they develop advanced liver disease or liver cancer. Current guidelines recommend that people with NAFLD who are most at risk for liver cancer be screened by ultrasound and lab testing every six months to measure disease progression.

But figuring out who those patients are is like finding needles in millions of haystacks.

Our recent study showed that the new blood test, developed at UT Southwestern by Yujin Hoshida, M.D., Ph.D., and his colleagues, can successfully identify who needs increased liver cancer screening – and who can safely get fewer screenings. We also found that this biomarker changes during NAFLD treatment, providing information about whether the treatment is reducing liver cancer risk.

How the blood test identifies liver cancer risk

The blood test measures the levels of 12 proteins in blood samples from patients with NAFLD. In a clinical study, we used these panels to segment 409 patients into groups of high and low risk of developing hepatocellular carcinoma (HCC), the most common form of liver cancer.

During a 15-year follow-up period, 37.6% of patients in the high-risk group were diagnosed with HCC. No patients in the low-risk group were diagnosed. This information guides screening recommendations for each patient.

The study also observed that the biomarker, including inflammatory molecules, can also be used to measure the effectiveness of existing and suggested NAFLD treatment options listed below for reduction of future liver cancer risk:

  • Statin medication to control cholesterol, which contributes to fat accumulation in the liver
  • Bariatric surgery, which can help reduce weight in individuals with obesity and type 2 diabetes
  • Diabetes medications that also help patients with obesity and type 2 diabetes achieve blood sugar control
  • IDO1 inhibitor, an experimental medication in development, that reverses the high-risk pattern of the blood-based biomarker in experimental models.

How we help patients reverse or cure NAFLD

The liver is the body’s largest solid, internal organ. When fat builds up on your liver, it’s like getting a burn on your skin. It causes redness and heat, which is a sign of inflammation. Repeated burns lead to scars and possibly skin cancer. That’s essentially what NAFLD does to the liver.

Over time, the inflammation and scarring can damage the liver and result in chronic liver disease, cirrhosis, or liver cancer. But just as we can treat burns, we can help patients reverse NAFLD progression and sometimes cure the disease to reduce liver cancer risk.

There are currently no medications specifically approved for the treatment of NAFLD. However, UT Southwestern is leading and participating in clinical trials for a variety of medications that we expect will one day be approved to treat fatty liver disease.

Until then, we do have approved therapies that can control diseases that are known risk factors for NAFLD, such as:

  • Overweight or obesity
  • Type 2 diabetes
  • High blood cholesterol/triglycerides
  • Metabolic syndrome
  • Sleep apnea, which can increase insulin resistance and inflammation
  • Older age

With most patients, NAFLD treatment focuses on weight wellness and optimizing risk factors. The liver is one of the first places where excess fat gathers, and it’s one of the first places patients who have NAFLD lose fat. Shedding just 1-2 pounds a month can lead to positive changes in patients’ liver chemistries – in the future, the new blood test will give us even more specific outcome estimates. UT Southwestern offers multiple avenues of support for weight management, including:

  • Guidance from dietitians with advanced training in overweight and obesity nutrition
  • Weight Wellness Program, which provides personalized coaching, medication management, and ongoing education for lasting results
  • Bariatric surgery, which has shown the potential to reverse metabolic disorders and systemic inflammation

Related reading: Fighting fatty liver disease – the No. 1 risk factor for women's liver transplants

The future of NAFLD and liver cancer care

As NAFLD and liver cancer rates rise, UT Southwestern is laser-focused on strategies to buck the trend. In August 2022, the National Cancer Institute (NCI) selected UT Southwestern to lead an effort to seek and validate new biomarkers to stratify liver cancer risk, identify and address health equity disparities, and improve early cancer detection.

Today, all patients with NAFLD go through a standard process for liver cancer risk assessment. Our new Clinical Validation Center will identify ways to personalize ongoing follow-up, allowing us to catch early-stage cancers more effectively.

The NCI initiative, along with our new blood test and the increased use of anti-obesity medications, could help turn the tide on liver disease.

Above all, these new developments will empower patients with information about their liver cancer risk and give doctors more dependable insights for personalized NAFLD management and liver cancer prevention.

If you have been told you have fatty liver disease, or believe you are at risk for NAFLD, and are interested in being seen by one of our liver specialists, please reach out to the UT Southwestern Liver Clinic at 214-645-1919 or request an appointment online.