Physicians: Keep Watch for NASH among Your Patients

Nonalcoholic Steatohepatitis (NASH) is, by far, the most prominent liver disease, even exceeding all viral hepatitis combined together. It is also becoming the most frequent etiology of liver cirrhosis. Despite this, NASH is still a widely unrecognized disease, not only by patients affected by it but also by physicians. All physicians should be aware that many of their patients may have undiagnosed NASH (ICD-10 code K75.81), which may have even progressed to NASH cirrhosis.

Why NASH is so often overlooked

NASH is often unnoticed because the liver inflammation of NASH remains asymptomatic for many years. Many patients first learn of their disease when it has already advanced to the cirrhotic stage. The story of Wayne Eskridge, a cirrhotic NASH patient who learned he had cirrhosis after a gall bladder operation, is a good example of the confusion and misdiagnoses that NASH cirrhosis patients usually experience. Eskridge founded a highly regarded non-profit organization to educate others on NASH and cirrhosis.

The steatohepatitis of NASH is a consequence of accumulation of fat in the liver, mostly fatty acids but also cholesterol. These fatty acids, transported through the bloodstream as triglycerides, become toxic to the liver and trigger a chronic inflammation. The reason why is not yet clearly understood, but it is the subject of active research.

It is also probable that the free cholesterol present in the liver of NASH patients is adding to the injury. It is well known that free cholesterol crystals are extremely immunogenic.

It is important to remember the accumulation of fat in the liver is not “normal.” The storage of fat is not a physiologic function of the liver. In NASH, the adipocytes are overwhelmed, and the excess fat distributes to the liver, a phenomenon that creates steatosis or fatty liver disease. With time, steatosis may lead to NASH and, ultimately, to liver cirrhosis.

While thin people can get NASH, generally NASH is a disease of obesity. It particularly afflicts people who are overweight or obese and suffer from type 2 diabetes. With more and more of the world’s population struggling with obesity and diabetes, there are more and more people with NASH. Physicians should understand that, if they are seeing an overweight patient, there is a strong chance the patient has fatty liver disease, NASH, or perhaps even NASH cirrhosis.

How to recognize NASH in a patient

There are three simple diagnostic tests to determine if a patient is likely to have NASH:

• Visual inspection. If a person overweight or obese — particularly with an abdominal obesity, the so-called android form of adiposity — steatosis is probable and NASH is possible
• High hemoglobin A1c. The risk of NASH increases substantially with diabetes 2, even with pre-diabetes. NASH has reached such a high incidence among diabetics that it could be considered a target organ for the complication of diabetes, just like the eyes, the cardio-vascular system, the kidneys, or the peripheral nervous system
• Metabolic syndrome. In addition to obesity and diabetes, NASH patients are frequently hypertensive and dyslipidemic

Multiple tests are now available to further establish the diagnosis of NASH. A simple liver panel showing a slight increase in transaminases further raise the suspicion for NASH and helps to prescribe non-invasive tests, notably imaging tests or ultra-sound based technologies, that will reinforce the suspicion:

• Fibroscan. Transient elastography measures vibration velocity within the liver as an indication of liver stiffness. The higher the stiffness (measured in kiloPascals), the higher the chance that cirrhosis is present
• Liver ultrasound. Evaluates the texture and dimension of the liver. Can determine if a liver appears cirrhotic
• MRI-proton density fat fraction. Evaluates the amount of liver triglycerides. Abnormal when more than 5% of the liver is made up of fat. This test does not differentiate between NAFLD, NASH, or NASH-cirrhosis

There is a lot of debate currently over the need to perform a liver biopsy to establish a diagnosis of NASH. Liver biopsies are not routinely recommended in clinical practice, but they are often a requirement to participate in the clinical trials currently performed to evaluate potential NASH and NASH cirrhosis therapies. None of these treatments have reached the market yet, and clinical practice might be reshaped in the future with the first drug approval.

About the Author

Dr. Pol F. Boudes, a dual citizen of the U.S. and France, has more than 25 years of experience in clinical drug development in immunology, endocrine, metabolic, orphan, and liver-related diseases. He is currently Chief Medical Officer of Galectin Therapeutics (NASDAQ: GALT), the leading developer of therapeutics that target galectin proteins to treat NASH cirrhosis and cancer.