The FINANCIAL — The ADVANCE (Accelerating Discovery: Actionable NASH Cirrhosis Endpoints) study will follow 200 patients with cirrhosis – scarring caused by long-term damage of the liver – to uncover why some patients experience liver failure or develop liver cancer.

Researchers from the Universities of Edinburgh and Newcastle hope their findings will lead to earlier diagnosis and the development of a first-ever approved medicine for cirrhosis.

Urgent need

It is estimated that more than 440 million people worldwide live with a condition referred to as non-alcoholic or metabolic dysfunction-associated steatohepatitis (NASH/MASH) – an inflammatory liver disease that is caused by accumulation of fat in the liver.

Over time, this causes scar tissue to form, which leads in many cases to liver cirrhosis. This can result in serious complications, including liver failure or liver cancer, and may result in the patient needing a liver transplant.

Ongoing assessment

The global study will enroll patients who have been diagnosed with or are thought to be at risk of advanced cirrhosis due to fatty liver disease.

Participants will initially undergo a biopsy to collect a small sample of liver tissue so that detailed changes in how genes are activated in the liver can be assessed.

Blood tests and MRI scans will be performed at regular intervals over the next two years. The data generated will allow researchers to see how disease-related changes evolve in the body as cirrhosis progresses.

The study is funded by pharmaceutical company Boehringer Ingelheim, and researchers will be supported by the University of Edinburgh’s commercialisation service, Edinburgh Innovations.

Liver disease has reached epidemic proportions worldwide. Therefore, there is a huge need to develop potent, new treatments for liver scarring. To help address this, over the last several years we have harnessed a new technology in Edinburgh called single cell RNA sequencing. Using this new technology has allowed us to study human liver scarring in high definition for the first time, and we hope that this cutting-edge approach will allow us to accelerate the discovery of much-needed new treatments for patients with liver disease.

Professor Neil HendersonCo-lead of the study and Professor of Tissue Repair and Regeneration at the University of Edinburghnone
We aim to work out why, even at the most advanced stages of liver disease, there is substantial variation in how the disease progresses with some people remaining well for many years whilst others rapidly experience liver failure or develop liver cancer. Working internationally with our collaborators, we will then use this knowledge to improve how patients are diagnosed, and to help develop new medicines.

Professor Quentin AnsteeCoordinator of the study and Professor of Experimental Hepatology at Newcastle University and Consultant Hepatologist at Newcastle Hospitals NHS Foundation Trustnone

Nonalcoholic Fatty Liver Disease

Fatty liver disease means that you have fat inside your liver that can, over time, affect liver function and cause liver injury. People who drink too much alcohol may also have fat in their liver, but that condition is different from fatty liver disease.

Health care providers divide fatty liver disease into two types. If you just have fat but no damage to your liver, the disease is called nonalcoholic fatty liver disease (NAFLD). If you have fat in your liver plus signs of inflammation and liver cell damage, the disease is called nonalcoholic steatohepatitis (NASH).

About 10% to 20% of Americans have NAFLD. About 2% to 5% have NASH.

Symptoms

Fatty liver disease is sometimes called a silent liver disease. This is because it can happen without causing any symptoms. Most people with NAFLD live with fat in their liver without developing liver damage. A few people who have fat in their liver develop NASH.

If you have NASH, you may have symptoms that could take years for them to develop. If liver damage from NASH leads to permanent scarring and hardening of your liver, this is called cirrhosis.

Symptoms from NASH may include:

• Severe tiredness

• Weakness

• Weight loss

• Yellowing of the skin or eyes

• Spiderlike blood vessels on the skin

• Long-lasting itching

NASH that turns into cirrhosis could cause symptoms like fluid retention, internal bleeding, muscle wasting, and confusion. People with cirrhosis over time may develop liver failure and need a liver transplant.

Who’s at risk

Health care providers don’t know the exact cause of fatty liver disease. But they think that obesity is the most common cause. Obesity in the U.S. has doubled in the last decade, and health care providers are seeing a steady rise in fatty liver disease. Although children and young adults can get fatty liver disease, it is most common in middle age.

Risk factors include:

• Being overweight

• Having high blood fat levels, either triglycerides or LDL (“bad”) cholesterol

• Having diabetes or prediabetes

• Having high blood pressure

Diagnosis

Fatty liver disease can happen without causing any symptoms. It’s usually diagnosed when you have routine blood tests to check your liver. Your health care provider may suspect fatty liver disease with abnormal test results, especially if you are obese.

Imaging studies of your liver may show fat deposits. Some imaging tests, including special ultrasound and MRI scans can help diagnose the disease and spot scar tissue in the liver. But the only way to be certain that fatty liver disease is the only cause of liver damage is with a liver biopsy. A liver biopsy involves getting a tissue sample of your liver with a needle. The needle removes a small piece of liver tissue that can be looked at under a microscope. Here’s how your health care provider makes the diagnosis:

• If you have fat but no inflammation or tissue damage, the diagnosis is NAFLD.

• If you have fat, inflammation, and liver damage, the diagnosis is NASH.

• If you have a type of scar tissue in your liver called fibrosis, you may be developing cirrhosis.

Treatment

If you have NAFLD without any other medical problems, you don’t need any special treatment. But making some lifestyle changes can control or reverse the fat buildup in your liver. These may include:

• Losing weight

• Lowering your cholesterol and triglycerides

• Controlling your diabetes

• Avoiding alcohol

If you have NASH, no medication is available to reverse the fat buildup in your liver. In some cases, the liver damage stops or even reverses itself. But in others, the disease continues to progress. If you have NASH, it’s important to control any conditions that may contribute to fatty liver disease. Treatments and lifestyle changes may include:

• Losing weight

• Medication to reduce cholesterol or triglycerides

• Medication to reduce blood pressure

• Medication to control diabetes

• Limiting OTC drugs

• Avoiding alcohol

• Seeing a liver specialist

Some medications are being studied as possible treatments for NASH. These include antioxidants like vitamin E. Scientists are also studying some new diabetes medications for NASH that may be given even if you don’t have diabetes. However, you should only take these medicines after consulting with a liver specialist.

Complications

The main complication of fatty liver disease is the progression of NASH to cirrhosis. Cirrhosis means permanent scarring and hardening of the liver.

When to call the health care provider

If you’ve been diagnosed with any fatty liver disease, let your health care provider know if you have any symptoms that mean the disease is getting worse. These include fatigue, loss of appetite, weight loss, weakness, fluid retention, or bleeding.

Living with fatty liver disease

If you are living with fatty liver disease, learn as much as you can about your condition and work closely with your medical team. Since many medications can harm your liver, always let all your health care providers know about any medications you are taking. These include OTC drugs, dietary supplements, and vitamins. Other ways to manage fatty liver disease include maintaining a healthy weight, eating a balanced diet, getting regular exercise, and continuing to avoid alcohol.