Transcript
DR. DINANI: Hello, and welcome to our podcast. Over the course of three episodes we’re going to discuss a serious and often undetected liver disease, which affects nearly a quarter of the world’s population: nonalcoholic fatty liver disease, which we’ll refer to as “NAFLD.” The more aggressive form of the disease is called nonalcoholic steatohepatitis, which we’ll refer to as “NASH.” I’m your host Dr. Amreen Dinani, and I’m a hepatologist who specializing in liver disease at the Icahn School of Medicine at Mount Sinai in New York City.
Today, I’m joined by Dr. George Therapondos, the Chief of Hepatology at Ochsner MultiOrgan Transplant Institute based in New Orleans, Louisiana. We are happy to have Dr. Therapondos join us today to discuss the prevalence of NAFLD and NASH and the importance of early identification.
To start off, first I want to say thank you for joining us on this podcast, and we’re very excited to have you here today.
DR. THERAPONDOS: Thank you for inviting me. It’s a pleasure to be here.
DR. DINANI: I thought we’d start off by talking a little about what we mean by NAFLD and NASH, so we can familiarize our audience with what we’re actually talking about.
DR. THERAPONDOS: Sure. The term NAFLD, or nonalcoholic fatty liver disease, is really the umbrella term that includes, or that is defined by, the presence of excess fat in the liver. That amount of fat is defined as affecting more than 5 percent of hepatocytes, and that’s considered to be pathological. The more concerning part of this disease is nonalcoholic steatohepatitis, which only affects a subset of the overall patients affected by NAFLD. The presence of the steatohepatitis part implies that there’s inflammation, liver tissue damage, and fibrosis formation, which can lead to long-term liver damage.
DR. DINANI: That’s a great definition, and I’m assuming when we talk about fatty liver disease or nonalcoholic fatty liver disease we, just want to make sure that we’ve excluded not only medications that can cause fat in the liver but also rule out other things that can give us excessive fat in the liver, such as alcohol, hepatitis C, and some other genetic diseases.
DR. THERAPONDOS: I think we have to exclude other causes of fat in the liver, and the most common cause of fat in the liver is of course alcohol. That causes a very similar syndrome with liver damage, inflammation, steatohepatitis, and even cirrhosis.
DR. DINANI: Great. We hear this statement a lot, and I was hoping you could expand upon it. Why do we call NASH the “silent killer?”
DR. THERAPONDOS: Well it’s called the silent killer because it’s a very prevalent disease, and we can talk about the prevalence of the disease in the general population later on. It’s a very prevalent disease, yet the majority of patients who have it actually have very few symptoms. So, you may be walking around out there with some degree of fat in your liver or even with steatohepatitis or some degree of significant liver fibrosis, but you may have no symptoms. People think of patients with liver disease as having jaundice, perhaps having some problems with fluid retention such as ascites or edema, but in the early stages of this disease you may have very few symptoms. Sometimes you may have some vague symptoms such as fatigue, but these are very nonspecific things that a lot of us will have even in the absence of this.
[3:41]
DR. DINANI: Yeah, I totally agree with that definition of how we describe it. If I think about all the patients that I first meet with fatty liver disease, they look at me thinking that they have no idea what I’m talking about because they sit there pretty comfortable, feeling fine, and they literally have only been referred to me because there was some fat noted on their ultrasound or they have elevated liver tests, which we can definitely go into later on. It’s really, really hard to convince someone that they have something that could be so deadly and dangerous when they feel pretty well.
DR. THERAPONDOS: Yeah, it’s a little like hypertension. Most people with hypertension don’t have any symptoms. They’re only treated by the doctor because somebody has measured it, and the blood pressure is up. So, in similar fashion, somebody has measured the liver test, it may be a little abnormal, somebody’s had an abdominal ultrasound that shows a little of what appears to be fat in the liver, and then they’re referred to us for an opinion. They don’t feel unwell.
DR. DINANI: Right, I agree with you. Just to get a sense of the burden of disease, and what we’re really talking about in terms of population, or possible population, that could be affected—you know I mentioned that it affects 25 percent of the global population. Should we maybe talk about prevalence, and if we have information on the NAFLD and NASH prevalence?
DR. THERAPONDOS: Yeah, there are various estimates of the prevalence of the disease out there, but I think in general it is accepted that the global prevalence of NAFLD is about 24%, with some higher rates reported in places like South America, the Middle East (around 30%), Asia (a little less). Generally, when we’re talking about Europe and the US, we’re right around the 25% mark. There’s probably a little inaccuracy depending on the method of identification of this disease, but that’s the estimated prevalence.
DR. DINANI: I mean that’s pretty significant. We’re talking about 1 in 4 persons that we see will have some form of fatty liver disease. If you think about it in that term, that seems pretty significant.
DR. THERAPONDOS: Absolutely. We’re talking about at least 1 in 4, as you said. In some places it could be as many as 1 in 3 depending on the part of the country you’re in, or the actual country you’re in, and on the prevalence of the comorbidities such as obesity and diabetes. You may have a significantly higher prevalence.
DR. DINANI: Yeah. What about for NASH, which is the more aggressive form of this disease? Is the prevalence you think as high as that for just NAFLD in general? Do we have better data for NASH?
DR. THERAPONDOS: Again, the estimates can vary depending on the study. Some studies in Europe have shown the prevalence of NASH as identified by the gold standard, which is currently a liver biopsy, to be as high as 69% in those with NAFLD. I think that in terms of the overall population in the US, there have been some estimates that place the prevalence of NASH itself as up to 10% of the total US population, which is pretty significant.
[7:10]
DR. DINANI: Yeah. Because then again your denominator, or what you’re really sampling, you already have a pretty high suspicion of them having NAFLD, so the population that you’re sampling is not really a sampling of the general population. Yeah, I think I agree with you. It’s probably an underestimate. There’s probably more undiagnosed NASH and NAFLD that’s out there.
DR. THERAPONDOS: Yes, absolutely.
DR. DINANI: So, one of the things you alluded to is that you mentioned obesity and Type 2 Diabetes as being two risk factors. Do we know anything about obesity and Type 2 Diabetes like does that increase our risk for NASH? Do we have any prevalence data on that?
DR. THERAPONDOS: Absolutely. Again, having these comorbidities certainly increase your risk of having NASH. I think going back to the definition, as we said, NAFLD is the overall umbrella disease and NASH is the subset of people who have the more serious disease, which is more likely to progress to advanced liver disease. I guess as hepatologists, we are more concerned with the people who have the more advanced form of the disease, NASH, which is more likely to progress. But, when we are looking at the patients with NASH, they are much more likely to have diseases such as hypertension, hypoglycemia, Type 2 Diabetes, and obesity. You know, the prevalence of these comorbidities ranges from about 50% to 80+%. So, having one of these other comorbidities is also a risk factor for having NASH as well.
DR. DINANI: So, not only having the presence of metabolic syndrome, but having even just the individual components of metabolic syndrome can contribute to not only your risk of having NAFLD, but specifically obesity and Type 2 Diabetes can increase your risk of having NASH, right?
DR. THERAPONDOS: Exactly. Yes.
DR. DINANI: You know when I think of risk factors, you know, there’s ones that your kind of dealt with, cards that you’re dealt with, such as genetics, gender, and ethnicity, and then I think about the ones that are more modifiable, like the things we’re talking about – obesity, diabetes, things like that. Do we know anything about any genetic associations or any ethnic groups that this disease might be more prevalent in, or that we need more information on?
DR. THERAPONDOS: There’s certainly some genetic predisposing factors associated with NASH. I think none of the genetic tests that we have available are particularly useful in clinical practice right now. In terms of ethnicity, we do know that Hispanics have a pretty high rate of NASH, a much higher, well, not so much a much higher, but definitely higher rate of NASH than whites and African Americans at least in the US. Race and genetics do play a big role.
DR. DINANI: If I understand this correctly, for Hispanics there might be an increased risk of you having certain gene factors that accelerate and increase your risk of having NASH and fibrosis. There’s even some suggestion that some of these genes that have been identified could also increase your risk of hepatocellular carcinoma (HCC), but like you said, these aren’t things we currently see in clinical practice. I think that with the evolving precision medicine and personalized medicine, this might be something that we’ll be seeing down the road.
[10:40]
DR. THERAPONDOS: Yeah, and I think you’re raising another issue. Ultimately, a lot of these patients will progress to advanced liver disease. The accumulation of fibrosis will lead to cirrhosis, and some of these patients will develop decompensated liver disease. Some of them will develop another silent killer, which is hepatocellular carcinoma. Although the individual risk of someone developing this if you have NAFLD, or even NASH, is relatively low, given that we’re seeing such a huge prevalence of this disease in this population, I think the actual numbers of people who will develop this condition in the future is going to be likely huge.
DR. DINANI: Yeah, and especially given what we also know about hepatocellular carcinoma associated with the disease. You know we typically associate liver cancer, or hepatocellular carcinoma, with people having cirrhosis. There is some really scary and daunting evidence out there that you don’t have to have cirrhosis in people with NAFLD to develop liver cancer. It’s not the majority of patients, but you know we start asking questions like how do we really risk stratify these patients and when do we start looking for liver cancer, which is a whole other aspect of this disease and burden we are going to see in the future. This can be very scary, not just as physicians who take care of these patients, but also for what it means for transplantation over the next 10-20 years.
DR. THERAPONDOS: Yes, absolutely. There are some studies out there showing a very significant prevalence of HCC in non-cirrhotic NASH, which is very concerning.
DR. DINANI: Right. So, putting this all together – we’re saying that nonalcoholic fatty liver disease, and NASH specifically, is a growing problem not just globally but also in the United States and other western countries as well. It’s also going to be one of the things that we have to deal with when it comes to transplantation and also liver cancer, and we also know that we have these associated metabolic comorbidities that increase your risk for having NASH. I guess the next question is why is it so important that we identify this patient population early, and why do we have such a hard time recognizing this?
DR. THERAPONDOS: So, these are my thoughts on this. I think that obviously as hepatologists we’re very interested in identifying people who are likely to progress with the disease to advanced liver disease, liver failure, and HCC; however, identifying these people also identifies that they are at risk from the other complications of metabolic syndrome such as the cardiovascular risk and Type 2 Diabetes complications. So, on one aspect we are hoping that our other colleagues will be able to manage these comorbidities more aggressively perhaps and reduce the cardiovascular risk that is associated with such patients. I think we’re having a lot of problems persuading our primary care colleagues and our endocrinologists of the importance of the liver manifestations of metabolic syndrome because they’re not as aware of the implications of NASH when it comes to what it really causes in terms of liver morbidity and mortality. I think we need to increase our education efforts with our colleagues in primary care and endocrinology and perhaps bariatric medicine. We just need to increase their awareness of this. There’s also a little bit of, being a little pessimistic, about their abilities to intervene earlier in the course of this disease. I’m not going to enter into our options of treatment, but I think this perceived lack of available treatments feeds into that negative perception.
DR. DINANI: Right. That’s definitely something we’re going to be discussing later on in this podcast series – a little about treatment even though there aren’t any pharmacological treatments just yet, but there’s still lots of things we can do to intervene in this patient population. Thank you for that. You mentioned a couple of things in terms of barriers for patient identification. I think one of the big ones that you mentioned is convincing or putting NAFLD on the radar of our dietologists, for instance, or even our primary care physicians but also other specialists like our cardiovascular disease and bariatric surgeons. What I find very interesting also is that we have really great society guidelines. The American Association for the Study of Liver Diseases (AASLD) that actually do not explicitly recommend screening the general population for NAFLD, but also our guidelines don’t tell us that we should be screening Type 2 Diabetics and the obese population either. So, besides society guidelines not mentioning that, we also don’t have a buy-in from some of our colleagues. Do you think there are any other barriers to patient identification that we haven’t discussed?
[15:56]
DR. THERAPONDOS: Well I think patient hesitancy in coming forward for further testing. I mean the majority of patients who do not show up in my clinic… I mean most patients when they get referred to a liver specialist do show up, but of the small number of patients who do not show up, they tend to have NAFLD, and they perceive it as a less important reason for going to the doctor. Whether that’s due to prohibitive costs for turning up, or whether it’s because they just don’t feel it’s important enough, I don’t know. The patient doesn’t feel unwell, and they don’t really see a huge rush to come to the liver doctor because of this.
DR. DINANI: Right. Sounds like we have to put a lot of effort into both patient education and also physician education, or clinician education, on why we think this is so important – not just from a liver standpoint, like you mentioned. One of the things that really affects morbidity and mortality in this patient population, especially in those that do not have advanced fibrosis, which to be completely honest is a huge bulk of this population, is cardiovascular mortality and Type 2 Diabetes-related mortality but also non-liver related malignancies, which we didn’t really talk about. We know there’s direct correlation between having obesity and non-liver related cancer, so putting those types of things on the radar of our colleagues becomes so much more important. We have a lot of work to do in that area too.
DR. THERAPONDOS: Yes, I agree.
DR. DINANI: So, what are you doing specifically to improve early identification efforts, and do you have any advice for other people in terms of what we can do to get the message out there in terms of increased awareness of NAFLD?
DR. THERAPONDOS: So, as a group of hepatologists over here we’ve gone up to various primary care physicians in the area. We’ve given some very brief lectures to educate them on the disease that we call NAFLD. We’ve made it easy for them to refer patients to us, and we generally have gone up to primary care physicians. We’ve also been targeting the local endocrinologists as well in order to make sure they’re aware of this condition, and they do appear to be aware of it… but I don’t think they have appreciated until now the seriousness of this, and therefore, they haven’t perhaps until now referred patients to us. Now that we see more and more patients with liver cancer, we see more and more patients with end-stage liver disease, especially now that hepatitis C has become a relatively frequent cause of transplantation, I think the relevance of NAFLD is increasing. People are beginning to appreciate that, but essentially what we’ve done is we plan to educate our other specialty providers on this condition within at least our health system. You know, we’ve done that to providers but also to the medical students and internal medicine residents who come through our system.
[19:18]
DR. DINANI: Those all sound like great initiatives that you’re taking, but it’s a lot of work for one person. I think that us as a hepatology, or subspecialty community, really need to start getting the message out there and need to start interacting with our colleagues, who are really treating the bulk of this disease, and start creating awareness. [We need to start] working with them, collaboratively with them, in terms of how can we focus on some of the other comorbidities to prevent progression of the disease and complications that people like you or I would start seeing. Do you have any final thoughts before we wrap up?
DR. THERAPONDOS: No, I think that it’s a condition that affects a large proportion of the population, so there is a lot of interest out there once you start going out there to try and spread the word. I think increasingly even when I’m talking about something that is vaguely related to fatty liver, there’s always some members of the audience who for personal reasons will ask me questions about fatty liver disease. So, I think that it’s becoming easier to spread the word, and I think people are becoming more aware of it, but I think there’s still a lot of work to be done out there to spur these people on to screen their patients and perhaps send us more for staging.
DR. DINANI: Right. I think the other part of this also is empowering them with the information in terms of: Who is it that you worry about a lot? Who is it that you don’t worry about so much? Which are the high-risk populations, such as those with Type 2 Diabetes and obesity, that probably need to be seen by a specialist for some form of scarring or fibrosis assessment? Really empowering our colleagues in terms of tools or pathways to follow in terms of how to manage or risk stratify this patient population would also be very important, but also raise the comfort level to take care of this population.
DR. THERAPONDOS: Yes, we agree.
DR. DINANI: Thank you, Dr. Therapondos, for your time today and really sharing your thoughts and insight into this disease. We really, really appreciate this. As a reminder, this is one of our three-part podcast series to increase education and awareness around NAFLD and NASH. Please join us next time to discuss noninvasive testing and diagnostics for NAFLD and NASH. This is a podcast series that was developed by NASHNET, which is a global center of excellence network, really dedicated to improving NASH care delivery. Thank you again, and please tune in next time. Thank you.
