The Progressive Nature of NASH

Drs Viviana Figueroa Diaz and Norman Sussman discuss the progressive nature of nonalcoholic steatohepatitis and highlight typical patient factors associated with risk of progression.

Transcript

Viviana Figueroa Diaz, MD: The pathophysiology of advanced fibrosis in NASH [nonalcoholic steatohepatitis] is because of ongoing inflammation from fat deposits in the liver. This activates cells that, in response to the fat and inflammation, start depositing collagen in the liver and leave scars. The more scars that are left because of ongoing inflammation, the more fibrosis that develops. That’s when it becomes advanced fibrosis and, eventually, cirrhosis.

When advanced fibrosis progresses, it leads to cirrhosis. The concern with having cirrhosis is not only for liver failure, but also liver cancer [hepatocellular carcinoma]. We’re also worried that even with just advanced fibrosis, you could develop liver cancer. But most likely when it’s advancing to cirrhosis, that’s 1 of the complications that can happen from the natural course of advanced fibrosis in NASH.

Also, addressing the progression of NASH, if there are any other injuries to the liver, in terms of certain populations that have other liver diseases, if you have NASH combined with some viral hepatitis, or if there is NASH and the patient uses alcohol, the progression could be faster.

Norman Sussman, MD: NASH is a condition in which the liver has fat and inflammation. That’s what defines that condition. The inflammation frequently leads to liver injury with healing. In the course of healing, we start to see scar tissue. As that scar tissue progresses, it affects the liver more and more. The early and middle phases are nearly impossible to distinguish by a patient. We may see early hints in blood tests, but just looking at the patient and how they feel you will not get any idea of how advanced their fibrosis is until they reach a point when they have cirrhosis with complications. At that point, you would know definitively, but at that point they have fewer options in terms of getting healthy.

The rate of progression is quite variable, both within patients and within families. Some families have early and rapid progression. Patients tend to progress the longer they have the disease. We see some patients who have cirrhosis very early, but many times it’s patients in their 40s and 50s. It’s also very important to recognize that the rate of progression within a patient is not constant. You have people who go for years with very mild disease, but then as it progresses and as they get older, the rate at which fibrosis develops starts to accelerate. So it’s not 1 stage per 7 years. It may be much slower at the beginning and much faster as you get to the end.