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The liver is a critical organ that has many functions. It balances the body’s energy budget, filters blood, and metabolizes drugs, for a start. Since the liver is so imperative, it goes without saying that when the liver starts to fail, a lot can go wrong. It is widely known that excessive alcohol consumption can damage the liver, but there are also other pathways to liver damage.  One particularly dangerous pathway for liver disease is Non-Alcoholic Steatohepatitis or NASH which is the most severe form of non-alcoholic fatty liver disease. The exact cause of NASH is unknown.  

NASH is a disease characterized by an accumulation of fat in the liver coupled with liver enlargement due to chronic inflammation and cell death. It is difficult to diagnose NASH. The symptoms, tiredness and/or pain in the upper right side of the abdomen, are not very specific to NASH or helpful in diagnosis. Most often, patients do not have symptoms at all until the later stages of the disease. 

NASH is widespread, affecting between 3-5% percent of the worldwide population. It has been referred to as a modern lifestyle disease, with things like overeating and sedentariness contributing to it.

There are several risk factors for developing NASH:

• Female
• Aged 50+
• Heart disease
• High lipid levels (ie: cholesterol/triglycerides)
• High blood pressure
• Metabolic syndrome
• Overweight or obesity
• Type 2 diabetes
• Insulin resistance
• Genetic and environmental factors

NASH is a progressive liver disease, meaning it gets worse over time without treatment or lifestyle changes. The first step of NASH is fibrosis, where repeated scarring occurs. This scarring forms when the liver is repeatedly damaged and healed.  NASH patients develop more severe forms of fibrosis about twice as fast as those with alcohol-induced liver damage. In NASH, unlike with alcoholic liver disease, the cause of damage is not always known. Fibrosis is scarring that is reversible with treatment. 

If NASH progresses further, cirrhosis may occur. This is scarring and liver failure that is permanent, though people can live with it for years. In cirrhosis, the cells of the liver themselves suffer damage. The final two stages of NASH are hepatocellular carcinoma, a type of liver cancer, and death. Tackling NASH early on is vital to those suffering from this disease!

Unfortunately NASH is an understudied disease with few routes to recovery. Currently, the most effective treatment appears to be weight loss, accompanied by dietary and lifestyle changes. In scientific studies, this has been only achievable by about 50% of those with NASH. With this in mind, and only the early fibrosis stage of NASH being reversible, the search for medications that can treat NASH has been described as the “Quest for the Holy Grail.” There are currently no FDA-approved drugs to treat NASH. Several clinical trials exist and will continue to enroll and may lead to a treatment soon. If you have NASH, it’s important to consider participating in clinical trials to help find effective treatments. Find out which clinical trials are enrolling near you by visiting our enrolling studies page. 

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience

Sources:

Povsic, M., Wong, O. Y., Perry, R., & Bottomley, J. (2019). A structured literature review of the epidemiology and disease burden of non-alcoholic steatohepatitis (NASH). Advances in therapy, 36(7), 1574-1594.

Sharma, M., Premkumar, M., Kulkarni, A. V., Kumar, P., Reddy, D. N., & Rao, N. P. (2021). Drugs for non-alcoholic steatohepatitis (NASH): quest for the holy grail. Journal of Clinical and Translational Hepatology, 9(1), 40.