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Liver Matters: Why You Should Be Concerned about Fatty Liver Disease
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Released: November 14, 2024

Expiration: November 13, 2025

Neeraj Mistry
Neeraj Mistry, MD, MS

Ep 1: Unlocking the Fatty Liver Mistry

Liver Matters: Why You Should Be Concerned about Fatty Liver Disease

[00:00:09] Neeraj Mistry, MD: Hello, and welcome to Unlocking the Fatty Liver Mistry. My name is Dr. Neeraj Mistry. I'm the Chief Medical Officer of the Fatty Liver Foundation, and the pun was intended. We are going to unlock the mystery of fatty liver disease.

[00:00:24] By background, I'm a medical doctor and I'm a public health physician. And so, we're going to be dealing with fatty liver disease from a medical point of view, but also from a broader health point of view, looking at the context, the environment, the lifestyle, and the social determinants of health, which frames the context in which our patients live. So, brace yourself and let's go on this journey of unlocking the fatty liver disease mystery.

[00:00:49] Fatty liver disease is quite interesting, and it's a disease that now is estimated to affect a third of the world's population. But it makes us hearken back to our days at medical school, when we were in some sort of pathology laboratory, histopathology, looking under slides, and looking at these liver cells.

[00:01:10] And after we looked at fatty cells under the microscope, we probably never talked about or dealt with fatty liver disease after that. And,  rightfully so, because it's a silent disease, it doesn't manifest itself too often, and yet it is sort of living in the third of the population.

[00:01:29] so we're going to go through a series of episodes where we're going to demystify and break this mystery of fatty liver disease and really understand what is causing it. Why is it topical now? What is the pathology behind it? What are the new developments in terms of therapeutics and diagnostics? And, and how do we integrate this in our day-to-day clinical practice?

[00:01:52] So the first thing I'm going to do is talk about the liver. It's an amazing organ. I mean, it has so many functions. It has a synthetic function, a metabolic function, absorption, storage, detoxification, and it's one of the most forgiving organs in the body. We abuse it. We put a whole lot of substances in our body, from medications to alcohol to processed foods, and the liver just, you know, does its job on a day-to-day basis.

[00:02:21] And it works really, really well and is forgiving until it's not. And it's a sudden cliff that all of a sudden the liver's function deteriorates and that's when people manifest with disease. and so, that contributes to fatty liver disease being a silent disease. And here's what happens with fatty liver disease because of a series of lifestyle changes that we've gone through, in what is known as lifestyle or noncommunicable diseases. It used to be called diseases of affluence. And I'll touch a bit on that now on the impact, not just in industrialized or high-income countries, but the global impact of fatty liver disease, in low-income countries as well as middle income countries, but with All these comorbidities related to lifestyle. We are finding that they all converging on the liver, type two diabetes, problems of lipid, metabolism, which includes high cholesterol and high triglycerides, metabolic syndrome, and obesity, being the largest association of it. and the last report on the state of obesity in the United States showed an adult prevalence of close to 42%, obesity. Childhood obesity is also on the increase, somewhere in the range of about 28%, nearing 30%. So, these are all comorbidities or disease conditions that contribute to the development of fatty liver disease.

So, what happens, and if you remember back to that microscope slide, it was these vesicles or these vacuoles that were forming within cells, liver cells, and causing them to expand. Literally, these cells are getting fatter, and when these cells get fatter, there's some sort of tension on the cell membrane, and that induces a state of inflammation. So, from fatty liver disease, we then move to steatohepatitis. Hepatitis meaning inflammation of the liver. And this inflammation over time, like we have inflammation in any part of the body, forming a scab, it forms fibrosis in the liver. And this level of fibrosis progressive over time, and we'll go through these pathology stages in another episode. But once the fibrosis sets in motion, it can progress to a point of cirrhosis of the liver, and this is sort of advanced stage fibrosis where the liver architecture changes into this honeycomb pattern and results in liver failure because it replaces the complex liver architecture that does the synthetic absorption storage function.

[00:05:06] And once a person develops fibrosis, they are in a state of liver failure, which requires liver transplant. And we know that cirrhosis also predisposes to developing liver cancer, hepatocellular carcinoma. So, when it comes to the end stage, we find that the health system implications. The costs of liver transplant and advanced care becomes much, much higher.

[00:05:32] So we have an opportunity now to address fatty liver disease. and I'm using a really broad term, fatty liver disease, because traditionally we talked about non-alcoholic fatty liver disease and alcohol-related fatty liver disease. and there's been an entire change in nomenclature which we'll save for the next episode.

[00:05:52] But I want to go into why it's really important for us to deal with this now. So, there's a few things that have happened. And many of you as primary care physicians probably ask new patients, do you have a history of diabetes, or do you have diabetes? And the response you heard was probably, no, I don't have diabetes yet, and this is an ominous sign to show. That there's been a normalization of these chronic pathologies, these diseases of lifestyle, obesity, diabetes, hypertension, cholesterol, metabolic syndrome, are all what people are expecting to get. My uncle had it, my grandfather had it, I lost a brother to it. These are the typical stories that you would hear of patients. So, we have a state of health where there's normalization of these comorbidities that lead to fatty liver disease.

The next thing we know is that with every new threat to an individual's health, there's a reinvigoration of their interest in their health. So, with the normalization of all these other pathologies, if we show patients that there is a new pathological manifestation, there's a new opportunity of engagement and a re-energization in them taking care of their lifestyles. and so, if we show, and we have done community-based screening, Through the Fatty Liver Foundation, we found that when we show people a scan from imaging of their liver, and that showed fibrosis, there was a new sense of, 'Oh, I need to do something about this.' So that's another opportunity that we have.

[00:07:31] And then the third thing I think that's very important because when I listed all these comorbidities, these are exactly the same comorbidities for cardiovascular disease. And chances are people with fatty liver disease will succumb to the cardiovascular complications and the cerebrovascular complications of their comorbidities before they get to the stage of advanced liver disease. The reality is cardiovascular disease with the comorbidities will have an impact on morbidity and mortality with most of our patients.

[00:08:06] But here's the opportunity we have. If we screen for fatty liver disease. It is an early warning sign that you have complications that are resulting from these comorbidities. So, it offers a chance for us to screen patients earlier on, sensitize them, and take actions on lifestyle, therapeutics, and behavior change that will influence their outcomes.

[00:08:33] So I'm delighted that you had a chance to join me in getting an overview of fatty liver disease. In our next episode, we're going to go into detail about this change in nomenclature of Moving from NAFLD to MASLD, and I'll go into all these big definitions for these big acronyms,

[00:08:52] we're also going to be going to sunny San Diego, for the liver meeting, which is hosted by the American Association of the Study of Liver Disease, or AASLD. And this is the preeminent conference that brings together key opinion leaders, as well as hepatologists involved in research on diagnostics and therapeutics. And we're going to be hearing from them from this conference in our subsequent episodes. So, looking forward for you, to join us, strap in and let's unlock fatty liver disease mystery.

This transcript has been lightly edited for clarity.