Douglas Denham, DO, the medical director of Clinical Trials of Texas in San Antonio, Texas, talks about a new global epidemic disease that shows no symptoms and currently has no treatment.
Interview conducted by Ivanhoe Broadcast News in November 2016.
Fatty liver disease if you were just to describe and I was a patient and you were telling me what it is what would you say?
Dr. Denham: Fatty liver disease is an abnormal accumulation of fat in the liver cells in your body. We don’t have a real good feel for what’s the exact cause of it. The liver is a very complex organ, it does a lot of things; it is very involved in fat metabolism in both creating new fat and breaking down old fat. We’re not sure why it accumulates but it certainly seems to be related to a number of common conditions like hypertension, diabetes, lipid disorders, high triglycerides, and high cholesterol. It’s also due to obesity; when you’re heavy extra fat gets stored in the liver.
And that’s a problem?
Dr. Denham: That is a problem because those cells aren’t designed to have fat in them, they have other things they need to do and when the fat accumulates in the cell then that causes damage to the structure of the cell and how it functions. You then get inflammation and then the inflammation leads to scarring and damage to the cells. Eventually that cell doesn’t do what it’s supposed to do any more.
With a fatty liver you’re going from healthy liver to NAFLD and then NASH which is where that that comes in?
Dr. Denham: It’s a gradual progression. Fatty liver is one of those things that you don’t feel bad as it’s developing, it’s gradual. When you go from nonalcoholic fatty liver disease, NAFLD, you’re seeing this gradual accumulation. Then, generally, once it’s about five percent or so of fat in the liver, then that’s kind of into the diagnosis criteria. It’s a fluid kind of thing, but it’s this gradual progression of increased fat in the liver cells, that decreased liver function. We measure that in your blood when we do liver function tests, so you begin to see your liver enzymes starting to go up above normal.
What does NASH stand for?
Dr. Denham: Nonalcoholic steatohepatitis.
At this point you’re kind of flirting with the danger zone for fatty liver disease.
Dr. Denham: Again, it’s a progression. Everybody is a little different. Your liver has a real capacity to kind of heal itself and to take a beating before you start seeing this thing. Someone who is Hispanic has a higher predisposition to this both genetically and due to lifestyle. Because, again, increased incidence of diabetes and hypertension in that ethnicity may have more problems or a more earlier onset of that than somebody maybe an African American who has a less likely genetic predisposition to that and an incidence of this.
We’ve seen a huge growth in this right?
Dr. Denham: You know it’s kind of a chicken and an egg thing. It’s one of those things because we didn’t really have a good form of diagnosis for this disease, the gold standard for this is still a liver biopsy. That’s a pretty aggressive test. I’m going to stick a needle in your liver pull it out send it to the pathologist and have them tell us what’s going on with the cell specimen. We haven’t had a good way to access it and then we don’t have a treatment for this disease yet. The only treatments we’ve ever really been able to tell you is: “you need to lose weight, you need to get your diabetes under control, you need to get your cholesterols under control.” All these other contributing factors to it. But we didn’t have a pill to say this is specifically to make the fat in your liver go away or the scarring to get better. We haven’t had that. It wasn’t until about 2013 that the FDA here in America came out with kind of a pathway to start developing drugs for the treatment of this.
That’s pretty surprising.
Dr. Denham: Well again, I think it’s one of those things that as we begun to realize you know what’s going on with it and see it more and the incidence is increasing too. I think that kind of goes along with our increase in diabetes, our increase in obesity in this society.
It’s like it matches up almost.
Dr. Denham: It does, I think there’s a lot of parallels to this.
One of the things I think is interesting about this there’s no—I don’t have symptoms like let’s say I have fatty liver which I may well have, there’s no symptoms.
Dr. Denham: You may be getting to you know you have a little increased girth but you’re not going to have liver pain. Those kinds of symptoms are the kinds of things that don’t show up until cirrhosis, the end stage of this kind of thing. Then, at that point in time, we really are stuck because we don’t have treatments for that. The only treatment for cirrhosis right now is liver transplant. There’s a long list of people on liver transplant and a lot of people that never make it to that because they die of the consequences of the liver disease.
When I go to my doctor and say I’ve got this I’ve got that, should I ask my doctor to check for that?
Dr. Denham: I think it’s certainly something to have a discussion about and see. Particularly say if you have that kind of predisposing you are overweight, you have diabetes, you have hypertension, you have cholesterol issues, and I think it’s something to talk to them about. Most physicians are going to do your annual blood work; they’re going to get a complex metabolic profile which is going to do kidneys, liver it’s going to look at your liver enzymes and functions. We may see a gradual elevation. If we saw that you didn’t really have it, I’m not going to diagnose you, if your liver functions are above normal I’m not going to say, “You have NASH or you have NAFLD.” It’s something we’ve tended to follow to kind of see a gradual progression, is it getting worse? Then implementing dietary lifestyle changes; getting back to the basics. Like I said, the only treatments we really have are: make you lose the weight, get have the body get the fat out of the liver and back to where it’s supposed to be and buy some time.
What kind of trial are you working on here; this is for a medication that could actually treat fatty liver because there is not one that exists. So what are you guys looking at right now?
Dr. Denham: We’re looking at several trials and we have some others that we’re looking at. How much fat is in the liver and then trying the new medication out on it, then, going back and repeating liver biopsies, and MRI scans to see if they’ve been able to actually reduce the amount of liver fat that we see on the scans.
The medication itself is going to be in the liver trying to reduce the fat?
Dr. Denham: It’s an oral medication that you’ll take that will work through the liver to try to reduce the amount of fat in the liver.
This is Phase I?
Dr. Denham: Yes, it’s a Phase I.
Phase I okay.
Dr. Denham: Phase I trials can kind of be scary. It’s not as aggressive as some Phase I trials, it’s not a first demand type of trial so we have some safety data and things like that. It’s not as like a new, brand new drug that has never been in humans before.
What are you seeing so far or is this a point where you can say what you’re seeing?
Dr. Denham: Actually, we haven’t really seen any of the interim data or anything like that yet to really know what’s with this particular trial. We’re getting another one, we’re just getting started on.
This is really in the new phase?
Denham: Yes, yes.
If this were to work and this drug is to work how would physicians if there are not symptoms and they’re not doing the testing. I mean obviously if this is going to work they’ve got to hit you pretty early here like the NAFLD the nonalcoholic thing. If there’s no symptoms and they’re not testing for it how do they know where to prescribe the drug? It seems like they might wait until it’s too late.
Dr. Denham: I think this is something that we’re going to start working on as physicians on how are we going to treat this. That’s what part of the studies will show us, is what are our timelines, what should we expect when we talk to the patient about taking this drug. What’s the course of therapy? You’re going to have to take this for a year and then things will be great. Is this a lifetime therapy? Those kinds of questions. I think what’s interesting with the two studies that we’re doing is imaging. Because again, the gold standard is liver biopsy to diagnose it, it’s not a benign procedure. People can get into trouble here bleeding. They’re also looking at MRI scans, they’re looking at a thing called fibro scan, which is kind of an ultrasound looking at the elasticity of the liver. They’re using a parallel track here in terms of, we’re going to do the biopsy see what the liver cells actually look like to give us a feel for what level they are. We’re also going to do imaging studies. Then hopefully they’ll begin to correlate this image goes with this level of disease. That will be another way for us to begin to really more easily diagnose how it goes.
This is really in its infancy it feels like.
Dr. Denham: This is something new for us. It’s going to be an area where we’re going to be depending on treatment guidelines that will be established as we go along. Hopefully it will be awareness to the populace. This is something we need to be aware of it and get it treated earlier rather than later. I think it’s interesting when you look at the literature and see where our people are going in terms of treatment with this. Some people are targeting it early and some people are targeting the later stages so it causes scarring and inflammation. We may end up having treatments for early studies, early folks and late folks too, so it will be interesting to see where that goes.
Is there anything you’re hearing here that you would ask in addition and is there anything you want to add?
Dr. Denham: The family practice doctor in me would say that when you’re talking with your physician, or if you’re concerned about this, or again if you have some of these conditions: if you have hypertension, if you have Type II diabetes, if you’re a little heavier than you should be that’s maybe something to write on your list and go in next time you see your primary care physician ask him. Say: “hey, I’m hearing stuff in the literature about this fatty liver stuff, or my friend got diagnosed with fatty liver is that something I need to be aware of. Or you know that kind of thing.” Asking the questions sometimes is the first step in getting some information and getting evaluation. Then you can explore those options. If you’re not satisfied with your physicians answer you can go see another physician.
Can you talk a little bit beyond Cirrhosis, that it can lead to cancer which is really serious. Past Cirrhosis it can get even worse, tell me about that.
Dr. Denham: It’s important to understand that if a nonspecific is going on initially, but progresses, it can go to cirrhosis which is not a good thing. From Cirrhosis we actually can get in to people who have cancer as a result of this. Hepatocellular carcinoma is not a good thing to have. I think it’s something that we as physicians certainly need to be a little bit more aggressive in looking for this and helping you. But again, as a patient I you need to take the bull by the horns and ask those questions because this does have negative side effects down the road. Certainly the hope is that we’ll find a medication that will help us treat this early on so we don’t go down that road where you’ve developed cirrhosis and possible cancer. That’s still a ways off with the research. We’ve got a few years yet that we’ve got to figure this all out. I think being your own advocate with your physician and asking those questions.
Do you want to mention the age, is there a typical age of onset? You want to touch on Hispanics, that Hispanics are more likely develop it?
Dr. Denham: Age wise I don’t really have a good feel for age numbers other than saying that we are starting to see more liver issues in adolescents in children now.
And why do you think that is?
Dr. Denham: With the increased issues of childhood obesity we’re seeing a lot of other disease states that we weren’t seeing normally in children. They were more adult types of diseases. This is certainly an issue again if your child is overweight, if you’re Hispanic descent; you have an increased propensity for this genetically so that’s something to be aware of. Certainly if there’s a family history of these kinds of issues I think are things that you need to broach again the topic with your physicians. Just ask him, open the dialog with him. Honestly physicians have so many things going on in the visit that sometimes it’s hard to ask or even think about those kinds of questions without the patient sitting in front of them saying something. Again, if you have a Hispanic descent you have an increased risk because of some genetics going on and so that’s something to ask about your child or yourself.
END OF INTERVIEW
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