NAFLD/NASH thought to Drive Cardiovascular Death, Researcher Explains

August 27, 2020

Interview: The liver disease itself, and not the associated metabolic dysfunction, may lead to CV death in these patients. Seth Baum, MD, is involved in research for a treatment.

Evidence is accumulating that links nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) directly with cardiovascular death. There currently are no medications approved specifically to treat either condition. But, Dr Seth Baum, founder and CEO of Excel Medical Clinical Trials, LLC explains there are close to 40 new drugs in development. He talks here about the growing prevalence of the disease and the research dedicated to its treatment.

The following transcript has been edited for clarity and length.

Patient Care: I understand that in addition to liver, morbidity and mortality associated with NAFLD/NASH, there is an accumulating body of evidence that shows that cardiovascular risk is very high in these patients and, in fact, the driving factor for death and many of them.

Seth Baum, MD: Yes, you're right. And you're one of the few people who knows this. Seriously, it's not well known throughout many circles of medicine.

So just as a backdrop, you know, I do clinical research that's my main thing now, has been for the last several years and a very large area of our research is in non-alcoholic steatohepatitis.

So there are over 40 drugs in development. And, you know, so many, many drugs, many mechanisms of action being looked at, to treat NASH. And the reason that so many drugs are in development is that we don't have a drug that's been approved for NASH and NASH is increasing in prevalence. Twenty-five percent of our population, maybe a little more, has non-alcoholic fatty liver disease, and somewhere between 5 and 7% of our population has actual NASH. And NASH, unfortunately, can ultimately lead to cirrhosis, or hepatocellular carcinoma. And yet it's prevalent and NASH and NAFLD are 2 of the liver diseases that are expected to rise significantly over the next 5 to 10 years. NASH is overtaking all other causes of, of liver transplant. So, cirrhosis from NASH is becoming the number one cause of liver transplant.

When you look at the typical NASH patient, that person tends to be metabolically deranged, if you will, you know, central obesity, insulin resistance, high triglycerides, a real atherogenic dyslipidemia with a high number of LDL particles or apoB, low HDL. So, this tends to be somebody about who you would say, “Well, you know, this is an individual who is already at risk for cardiovascular disease.” But when these other comorbidities have been controlled for in studies, it is really looking like there's something inherent in the NASH process that's leading to an increased risk of cardiovascular death.

Knowing that you might say, “Well 'm sure we have great guidelines about how to manage these NASH patients to avoid cardiovascular death.” And the answer is no, we don't have those great guidelines. So that's something that's really missing.

And most clinicians don't really look at NASH patients as cardiovascular patients, and they should.

Studies have been done looking at, for example, this was done in South Korea, a group of patients who at baseline had calcium scores of zero and then separating the NAFLD and the non-NAFLD patients based on ultrasound of the liver and then following them for several years and seeing who developed the calcification—and the fatty liver ones developed much more calcification than the non-fatty liver ones.

You know coronary calcification is a great tool to assess cardiovascular risk; it's our best noninvasive tool to assess that. So that's very meaningful.

The important thing, the takeaway message here for primary care practitioners is that when you see a patient who may have fatty liver, you should look for it. Look for it either with an ultrasound of the liver, an MRI, fiber scan if that's available; look for the possibility of steatohepatitis, look for the possibility of fibrosis. Understand that there are many clinical trials that are ongoing and look around your vicinity to see whether you can get these patients in clinical trials because that's a hope for them—both immediately and in the future.

Probably more importantly, let the patients know, “You have a fatty liver and this can lead to, not just cirrhosis and hepatocellular carcinoma, which are bad enough, but also to cardiovascular death, or arrhythmia, or cardiomyopathies—those are also associated.” Let the patient know that and then try to activate the patient to improve. Improve means lose weight, manage the lipids properly, exercise, drink less alcohol. These are the things that we can do. But we need to activate everybody; the physicians need to be activated and the patients need to be activated. And the only way we do that is through knowledge, by understanding the risk and how to identify this, and then ultimately how to prevent the events from occurring.