Liver and Gallbladder Health: From Fatty Liver to Bile with George Nikias, MD

Welcome to The Perfect Stool: Understanding and Healing the Gut Microbiome. This is your host, Lindsey Parsons. Today I'll be speaking with gastroenterologist George Nakias, MD, who is a graduate of New York Medical College. He completed a residency in internal medicine at North Shore University Hospital and Memorial Sloan Kettering Cancer Center, followed by a fellowship in hepatology at the Mayo Clinic in Rochester, Minneapolis, and a fellowship in gastroenterology at Memorial Sloan Kettering Cancer Center. Dr. Nikias is a member of Hackensack Gastroenterology Associates. But before our conversation, if you haven't yet followed or subscribed to the show, be sure to do so. And if you wanna get transcripts of the podcast, pop over to my website, HighDesertHealthCoaching.com, and sign up for my newsletter. You'll also get my free ebooklet called Finding Your Root Cause Through Stool and Organic Acids Testing when you sign up. And if you haven't yet done my quiz on which stool test would help you get to your root cause, you can find a link in the show notes and take that. Now on to the show.

Welcome to the podcast, Dr. Nakias.

Thank you very much, Lindsey Parsons. Happy to be here.

So I understand liver disease is your specialty. So can you give an overview of the things that go wrong with the liver and what the signs and symptoms are?

Sure. Well, so liver disease is a subspecialty of gastroenterology, and it's a growing one. And Can— are the patients we'll see with liver disease will range anybody from a person who feels well that has abnormal blood tests related to the liver, perhaps identified by their primary doctor or primary healthcare professional, to someone with severe liver failure, jaundice, life-threatening illnesses, and everything in between, including persons with chronic liver disease that are suffering the complications of that and may need evaluation for liver transplantation. And we can talk a little bit about the common liver conditions that people hear about or read about, as well as the less common ones. But ultimately, hepatologists, or physicians who have specialty training in liver disease, deal with all of these varied conditions that affect the liver.

Okay. So, yes, let's talk about those different conditions. And how they come about.

Why don't we work from sort of a common kind of everyday scenario in the clinic that we often deal with and we can expand from there? Because very often we'll see— well, yeah, we'll see well individuals that come to the office or the clinic with no complaints other than being told by their primary healthcare provider that they have abnormalities in their liver tests. And often they will seek further evaluation on the computer and learn of potential causes. And this, at the same time, this can also be a point of alarm. People have fears that perhaps the liver is failing or not functioning, but very often that's not the case. So a common scenario would be somebody who feels well, perhaps has some other health conditions, who has elevations in the typical liver chemistries. The AST and the ALT, as we typically define them, on the health panel or the metabolic profile that's done as part of a routine healthcare visit. Very commonly, those liver tests can be elevated. And one of the very common reasons in this country, and for that matter worldwide, is a condition called fatty liver, or as it's now being described as nonalcoholic fatty liver disease, which is now evolving something that's described as metabolic liver disease because we've learned that fatty liver really is part of a process that involves physiologic changes across the entire body. And the implications of that is important with regards to not just liver disease but overall health. And longevity.

And how does this come about?

Well, the common scenario, the common condition that exists with fatty liver is typically ele— weight above normal, or elevated body mass index, as we call it. The common theme seems to be central obesity, or abdominal fat, which we've now learned isn't simply a storage platform for calories, but an active, an active area for physiologic functions in the body. So fat isn't just an energy source in our body, but fat cells have a role in metabolic performance in us. That being said, individuals who are heavy, are at risk for fatty liver. With that, with the presence of fatty liver comes a condition called insulin resistance, which we now know, and I think many people recognize, eventually can lead to risk of diabetes. Those conditions, fatty liver, diabetes, can coexist with other findings including elevated circulating lipids and elevated high blood pressure, which all make up a condition called metabolic syndrome. So metabolic syndrome is a physiologic change in the body that very routinely exists with fatty liver. In fact, fatty liver can be the prequel, if you will, to the development of metabolic syndrome, diabetes, and potentially systemic changes in the body or, or complications in the body occurring from that physiologic change. So the drug— so the evolution is from individuals developing fatty liver, developing risk for diabetes, metabolic syndrome, high blood pressure, associated high lipids, and complications from that, particularly cardiovascular and other vascular diseases.

And will you typically see blood sugar or fasting glucose or A1C rise before you see the liver enzymes rise? 'Cause I've seen a lot of that without elevated liver enzymes.

I mean, I, I think that's the important, that's the important caveat there is you, if you have someone with elevated hemoglobin A1C, a diagnosis of diabetes, even if liver chemistries are normal, fatty liver very commonly exists. So there's really kind of an umbrella that covers everyone with fatty liver. There are those that have normal liver chemistries, that have fatty liver. There are those that have abnormal liver chemistries that also can. And then within that umbrella, there's a subset of individuals who have risk for liver disease, including hepatitis, liver scarring, and the complications of scarring, which would include cirrhosis and the complications of cirrhosis. So the way I sort of view it, it's kind of this, iceberg or this all-encompassing term fatty liver. And then within it, a subset of individuals with true risk for significant liver disease. So to go back to answer your question, you can have normal liver tests and have fatty liver.

Got it.

And then the bigger question is, you know, are those persons at risk or not at risk for liver disease? The answer is they are, but probably less so. If they have normal liver tests, but not always.

Okay.

That's where it gets a little bit tricky. Okay.

So obviously you're talking about the metabolic fatty liver and or non-alcoholic, but I'm wondering, I hear a lot of separation of the non-alcoholic fatty liver disease and alcoholic fatty liver disease, and I'm wondering if they play out differently other than the cause. And if the things that can mitigate or reverse those conditions are any different other than obviously one requires stopping drinking and the other one probably probably changing your diet and—

Yeah, I mean, I think that it's a good question and there's, and there's been a lot of, you know, the problem with fatty liver in general is that we don't have good treatments. And so it behooves us if someone is overusing alcohol to counsel them about, about reduction, if not elimination of alcohol, if they have fatty liver in general or risk factors or fatty liver, meaning if they're diabetic, if they have high BMI or high central abdominal girth, and they have excess alcohol use, we will intervene in that situation and counsel them. So then the natural history or the evolution of non-alcoholic fatty liver, and it can become— the tricky case is the individual who has maybe casual alcohol use, or what's considered casual. But also has risk factors for nonalcoholic fatty liver and has abnormal liver tests, you know, how do we counsel them to make changes to determine that we're having an effect on the other condition, right? As you said, Lindsey Parsons, you know, stopping alcohol or reducing alcohol is one very effective intervention for alcohol fatty liver. But how do we counsel someone regarding modest alcohol use or casual alcohol use if they have— if they have fatty liver incidentally. And so this becomes, it becomes a tricky thing to work through.

Yeah. So what do you tell patients about reversing fatty liver? Because I, I mean, I know how hard weight loss is and that for some people it just seems to be they're on and off diets their entire lives until they finally just reconcile themselves to their current weight because they realize the futility of that or, or, or adopt a more healthy attitude that their, that their health is what their goal is, not their weight. So I'm just curious, when people who have disordered eating, it's, it's so complex.

I think that, right. And it's a, I think first of all, the key is to, is to have them set goals that are realistic. So, you know, what I, what we do when we see them first and tell them they have this condition is first of all, reassure them that the vast majority of people that have fatty liver will not die of liver disease. However, And this is important, we tell them, is that, you know, you are at risk for vascular complication. So all the— and so the goal here is, as you said, total body health and achieving that. So, you know, if we sort of look at this in a two-pronged way, if we look at the evaluation of liver disease, you know, there are measures we take to stratify risk, to identify are they at risk for significant liver disease. And we can do that using Very simply, from looking at their blood tests, we can come up with a risk profile, what's called a non-invasive index. And if it looks like there's concern that those blood tests can't clearly exclude significant liver disease, then we have technology in our office that allows us to determine if there's a risk of significant liver disease using something called elastography. Elastography is technology that uses ultrasound to determine the stiffness of the liver. So sound is, is transported through the liver. A harder liver, a harder substance transports sound quicker. And so the speed of which the echo of that sound that's transported to the liver is measured. And if the speed is faster, then the liver is deemed to be harder and the fibrosis index or the E-score is higher on that Fibroscan test. And if that's somewhat— if that's identified, then we have a discussion about that risk and really begin to talk to them about the possibility of a liver biopsy to confirm it or really have a distinct discussion about intervention. Now going back to that intervention in terms of your initial, you know, the initial goal is giving them tangible, actionable goals to shoot for in terms of weight loss, because the vast majority of these individuals are— have above, above normal body weight. So the numbers we'll use to— that have been shown in studies to affect change in terms of liver fat and liver scarring are 7% of body weight and 10% of body weight respectively. So we tell them, look, the goal here is not dropping a huge amount of weight in a short period of time, but rather aiming to lose 70% of your body weight, which is, I think, realistically achievable for many people to see that. And that's been shown to reduce liver fat. Along the same lines, 10% body weight loss has been shown to have impact on liver scarring. So I think the goal is to really create a paradigm for success with tangible goals. And then the expansion of the extension of that is, well, the last, what diet do we use? And there's been some work in this and there's still, I think, is lack of clear clarity as to what the ideal diet is for fatty liver. But I will, but data seems to suggest that a Mediterranean diet really stands forth as the ideal diet, both from the standpoint of weight loss, weight maintenance, and potentially heart health. So I generally endorse a Mediterranean diet for these, these individuals.

I know I have seen people who are able to lose a lot of weight on a ketogenic diet and maintain it. But the problem that I've also noticed is that after a while, people are just dying for carbs. And so that it's just sort of unrealistic as a long-term plan, but an easier way of losing a lot of weight fast.

I know, I think you're right. And I think that I don't like to use the term diet because diet to me implies short-term, short-term intervention.

Correct.

Which is not pragmatic. And we know that, right? And any short-term intervention is bound to fail. So what I said was, look, just don't think about this as something you need to do for 3 months or 6 months or even a year. Think about it as something you're gonna do permanently. So make it achievable.

Right.

Change is slight. And the other big thing is, you know, is, is, is activity and encourage them, just look, go out and if you don't walk, just walk 5 minutes the first day and walk 10 minutes maybe the next week after that. So I think that what, what my view is, is that, you know, what I want to espouse is lifestyle changes that are permanent, but in order to be permanent, they have to be achievable. So if we set up unrealistic goals, at the outset, then they're doomed to fail. And I think that's the way they would— they should view the condition as one that's not going to impact them anytime soon. And so the intervention should be something for life because this condition moves slowly and is correctable provided the results are achievable for the long term.

Okay. Can you explain a little bit the different terms and stages of liver disease? So like you have fatty liver and I know there's cirrhosis, fibrosis, like what is— how does that progress?

Sure. So, if you look at, if we look at the condition fatty liver, well, 'cause, right, 'cause fatty liver is sort of all-encompassing. So the vast majority of persons with fatty liver have nothing other than fat in the liver. So if you took a specimen of liver from someone with fatty liver, straight with just fatty liver, and looked at it under a microscope, you would just see globules of fat. They can be large or small in size, but no associated inflammation. So that's an individual with fatty liver but without hepatitis. So you'll often hear the term NASH, N-A-S-H, used to define nonalcoholic steatohepatitis. In that case, and that represents about 25% of the total group of individuals with fatty liver, in that case, there is fatty change associated with inflammation. And from within that group, there is the highest risk of fibrosis, which is the term used to define scarring of the liver. And then fibrosis is graded along a kind of a well-defined staging score that moves from stage 1 to stage 4. Stage 1 being minimal fibrosis, stage 4 being cirrhosis. So cirrhosis and, you know, and all the kind of pejorative connotations associated with it, really is simply a way to define the end stages of a defined scarring pattern across all liver diseases, not just fatty liver. And individuals with cirrhosis can have an absolutely normally functioning liver. But what individuals with cirrhosis have is a context in their liver that puts them at risk for liver problems from a variety of insults.

And is cirrhosis evenly distributed or fibrosis evenly distributed throughout the liver? Or is it like there's a section of liver that starts to go bad and then it kind of spreads?

No, it's— so cirrhosis is something that impacts the whole liver. And that's often, you know, one of the big discussions when somebody comes, they need certain liver surgeries. Well, I have this problem. Can we just— if we cut the liver out, can the liver just— because I've heard liver can just grow. You know, can't, will it just grow back? And that's, you know, the, like the mythological, the mythological story of the, I forgot that it was, he stole fire from, stole fire from the gods and then he was doomed to have his liver eaten, but the bird would come back and eat his liver cuz it would grow back. That happens with a healthy liver. So if you have a healthy liver and you lose half of it cuz of surgery, for example, it will grow back to reoccupy the space that it existed before. A liver that's cirrhotic doesn't have that same capacity. So, so, so, 'cause cirrhosis is a uniform scarring process.

Okay.

Across the whole liver. Okay.

Okay. And, and fibrosis too, that's throughout the whole liver, right?

So, yeah. So fibrosis is, think about fibrosis is this kind of very spidery kind of scar tissue that intersperses its way through the liver. And cirrhosis is simply that spidery scar tissue becoming more dense. So dense to the point that normal liver tissue becomes encircled by it. Thick bands of it now encircle the liver. And that nodule appearance of the liver that we associate with cirrhosis is expansion and dense— and densening of the fibrosis that becomes cirrhosis.

Okay. And can you tell about the stage of liver disease from the ALT and the AST markers on the blood test?

No. So the AST and ALT markers can be— what the AST and ALT markers do is tell us whether there's potentially a liver disease or liver condition at play. So those tests are, if you will, they're screening tests for potential liver condition. The level of elevation of the test doesn't tell us how severe the liver disease is. The level of elevation doesn't tell us whether or not cirrhosis is present, although there can be certain patterns that might alert our attention to that. But someone can have normal liver tests and still have significant liver disease. So sometimes it is confusing. There's a disconnect there, right? Individuals will come to the office and say, I've been told I have cirrhosis, you know, but my liver tests were always, they were always okay, or maybe just a few points off, you know, how could this happen? Because it's not as straightforward as a link between the level of elevation of those tests and risk.

Are those tests testing how much the liver is currently being damaged as opposed to how much it has progressively been damaged?

Right. So that's a good question. Right. So intuitively you'd think that a higher elevation in those tests corresponds to more liver damage, and that can be the case. So Let's say somebody has hepatitis because they, they ate contaminated food and developed hepatitis A, for example. Well, those liver tests can rise dramatically, very high. You know, let's say a normal ALT for a healthy adult is between 25 and 30. In someone with a viral hepatitis, that number can rise as high as 1,000.

Oh, wow.

Yeah, which is, which is not something that's characteristic of fatty liver. So the level of elevation gives us a clue as to the cause, but not necessarily the severity because someone with hepatitis A can have a dramatic elevation in the ALT level and at the same time can have a normally functioning liver. And there's somebody that can have cirrhosis and liver failure and their ALT level can actually be normal or minimally elevated. Okay, so it tells us— so we get insights into the cause of liver disease by the pattern of elevation and the degree of elevation, but it does not always give us insights into the severity. Okay, right.

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Okay. Well, obviously it sounds like it's, it's not something that's consistent across people, but I'm just curious whether you, what kind of numbers you see on ALT or AST before people have complete liver failure, or is it just completely random depending on the cause?

Well, so again, so the diagnosis of liver failure isn't predicted by the AST or ALT.

Okay.

So the diagnosis of liver failure is predicted or is raised or the consideration is raised by a collection of symptoms and lab tests, including tests like the bilirubin, which is a byproduct of red blood cell destruction. That the liver is responsible to metabolize and handle. The serum bilirubin is part of that metabolic profile that we talked a little bit about, that chemistry panel. So the bilirubin level can be elevated. That gives us insights into whether the liver is functioning normally. The albumin level, albumin is a circulating protein in the blood that's produced by the liver. Lower levels of albumin suggest reduced synthetic ability. So the liver begins to fail. The ability to make albumin goes down. These are factors together with other symptoms or other findings that can raise the concern about liver failure. But the AST and the ALT can be normal or near normal and someone can have liver failure.

Okay.

And so with transplants, the donor base, I, I'm guessing is probably somewhat larger if you can cut off a piece of a liver and still have it regrow. So like if somebody gives up a piece of their liver, they might still be perfectly fine.

Well, yeah, then that's, in terms of a donor, yeah, that's the motivation is a living donor liver transplant. So the opportunity to donate a portion of a liver to another individual kind of works from that very virtue, which is that a healthy liver will grow back. So you can donate a portion of your liver to someone else because you don't need a whole liver to, to have a healthy life. And that healthy liver will grow over time.

Even the donated, the donated piece of healthy liver, or when you do a liver transplant, I assume you completely remove the diseased one and you put in the new one.

Yeah. With liver transplant, the whole organ is removed. That's right.

Okay.

Like, yeah, yeah. The whole organ's removed. And replaced with a new liver. And that's because, and we can talk a little bit about it if you like, is that the diseased organ, the complications of liver disease are manifold. Besides just not functioning in terms of the metabolic demands of the body, one of the other big problems of the liver is problems with high pressures in the main vessel, the main vein that feeds the liver called the portal vein. One of the complications of cirrhosis is high pressures in that vein. So in order to correct that, the native organ needs to be taken out because you'd think, well, gee, if you have a, you know, if you have a liver that's not, that's failing, why don't we just put a new liver and not take out the old one? But you have to take the old one out in order to address that other problem.

Okay. So is reversal of fibrosis or cirrhosis of the liver possible? Because I actually just, just published an episode, episode 89 with Dr. Barry Tan, who did a study on tocotrienols, which are the most active form of vitamin E. And in his fatty liver study, they did show fibrosis scores going down. So I'm curious if, if you, in your experience, the fibrosis scores can go down and, and if you've used the tocotrienols.

That's such a great question. It's actually, that's so that That very question is an area of very intense study, not just in fatty liver, but in liver— across liver disease in general. Because cirrhosis represents, as we've said, the end stage of the scarring or fibrosis process, right? So if we can interrupt or reverse fibrosis, then we can essentially eliminate the risk of cirrhosis and the complications of cirrhosis. So the answer is, is fibrosis regression possible? The answer is yes. And this has been shown across multiple liver diseases including hepatitis B where actually patients that have cirrhosis will have the cirrhosis regress. You know, the thought was always that scar tissue is permanent. Like if you have a, you cut your arm and yet wound forms and it's fibrosis, right? It's a response to, to injury. Well, the perception was always that fibrosis in the liver, that response to injury was permanent. And that actually has been shown to not be the case, that fibrosis in the liver is a dynamic process. So if you can correct the underlying cause, if the fibrosis is present and early, It's reversible. There's a, there's, again, we talk about this fibrosis to cirrhosis evolution. There is probably a critical point at which cirrhosis becomes so dense, there's so much scar tissue that despite elimination of the cause, that cirrhosis may not reverse. And we see this in a number of conditions. So hepatitis B, you can have cirrhosis, but if the cirrhosis is advanced and dense, treatment of the hepatitis, of the virus, you— control of the agent that's driving the inflammation will still not allow the cirrhosis to reverse. But, and this is actually really interesting, if you have somebody with hepatitis B, for example, and liver failure, and you put them on treatment, if they respond to the treatment and their failure— and the liver failure is controlled, there can eventually be liver healing. There's other conditions, for example, autoimmune liver disease, which is a hepatitis that can look just like a virus, but it's actually our own body damaging our liver.

Right.

Autoimmune liver disease, if controlled, fibrosis there regresses, shrinks away. So yes, so fibrosis is a dynamic process. Therotis, and is reversible. So fibrosis is a dynamic process. Potentially reversible. Cirrhosis, the end stages of fibrosis, is also dynamic. So early cirrhosis, right, those— that sort of spidery scar tissue, not too dense, reversible, shrinks away. Very dense to the point that the liver begins to have problems with blood flow through it and some of the other physiologic changes associated with cirrhosis, that may not be reversible. And this— the question is, you know, when is when do you sort of go over that cliff? When is the, when are the changes irreversible or permanent?

Yeah.

Not, there's, there's some very interesting work going on with that, trying to better identify people who are on that cusp to intervene more readily so that we can reverse it.

Yeah. Okay. So what causes gallbladders to stop functioning properly and create stones?

Well, gallbladder stones are the result of a change in the solubility of the contents in bile. So gallbladders don't stop functioning, but rather they suffer the consequences of their contents, which are stones or sludge. So bile is a solution. It's 95% water, but the other 5% is comprised of a variety of substances, including most— the, the, the biggest component is something called bile acids or bile salts. They're really critical in a variety of body functions, principally fat absorption—fat-soluble vitamin absorption, fat absorption—as well as other metabolic processes. So bile is composed of bile salts, cholesterol, phospholipids, proteins, and other solutes, sodium potassium like that. And this all kind of exists in solution. And the theory is that for a number of, a variety of reasons, the solution kind of falls out of its stable state and things begin to precipitate out. And those precipitants, for example, cholesterol or other components of bile, begin to lead to production of stones. And stones, which can often, exist without symptoms can rest in the gallbladder where they, where they just, they exist and there's no issues. If an individual has a stone and as a result of normal eating, the gallbladder squeezes to try to expel bile to assist with digestion, the stone could become stuck in the neck of the gallbladder. And this can, this is felt with source of pain, like pressure in the in the gallbladder itself, causes biliary type pain or gallbladder pain. And where will you feel that? The most common place is actually underneath the breastbone, but often radiating to the right, right upper abdominal area or the right flank, often after a meal, generally a fatty meal. So 30 to 45 minutes after a fatty meal. People can often have symptoms at night, which is, which is kind of curious because you're not eating at night, but People often complain of some kind of pain waking them from sleep. So gallbladder pain is a sign of gallbladder, again, not so much gallbladder spasm, but a pain related to gallbladder malfunction, if you will. If it's not treated, then the gallbladder can become inflamed or infected, which can lead to serious problems at that point. Yes. And that's called cholecystitis. Called what? Called cholecystitis. People often talk about, okay, you know, an infected gallbladder. That's the consequence of that problem or that issue.

Okay. And so how can people intervene at the first sign of problems to prevent it from escalating to where they have to have their gallbladder removed?

Right. Well, that's, that's the, you know, that's the tricky thing because it, it, because recurring attacks that are suggestive of Gallbladder pain typically warrant gallbladder removal. And the whole paradigm of gallbladder removal really was changed about 30 years ago when laparoscopic surgery redefined how the gallbladder is removed. So it turned an operation that used to have an obligatory long hospital stay, a risk of complications, into a straightforward operation. Now it's almost done. On an outpatient basis, people will come in in the morning and go home in the afternoon with their gallbladder gone. So laparoscopic surgery simplified the intervention for gallbladder problems. But there are people who will ask about non-operative interventions. And, you know, we'll talk to them. We'll say, look, you know, weight loss can sometimes facilitate Gallstone dissolution, the stones will dissolve. Although interestingly, paradoxically, rapid weight loss results in gallstones formation. So I'll say, look, if you lose weight, you know, yeah, which kind of goes back to this whole, I think is the idea of, you know, there's no quick fix at anything. You know, it should all be gradual and sort of, and sort of reasonable. But, but weight loss can help with gallstone dissolution. The other thing I will tell them is that, you know, is that if you have no symptoms, you don't need your gallbladder removed. So the presence of stones doesn't require gallbladder removal. There is medication that is approved and has been around for a long time that's actually a component of bile called ursodeoxycholic acid. It's one of the bile acids present in circulating bile. But it actually has the ability to dissolve gallstones. The problem is that it's not reliable in doing so. You'd have to be on it indefinitely. So it doesn't serve as an easy management option if somebody's having pain related to their gallbladder.

What about diet changes or eating things that help thin the bile?

There's no diet specific that will change bile composition. Ursode, that supplement will change the composition of bile. As far as diet, you know, typically fatty food will trigger attacks, gallbladder attacks. We will counsel people to perhaps have a lower fat diet, but it's not a durable fix, if you will.

Okay. I want to back up and ask about treatments for liver disease, because you did mention obviously that it is possible to reverse the fibrosis. So what kind of traditional traditional or, and/or non-traditional treatments can you point to?

Yeah, no, I think that's an important question. So if we look, you know, and we talked a little bit about the common one, which is fatty liver, and the way to reverse fibrosis with fatty liver is again, is aiming for, so aiming for weight loss. So weight loss does have the ability to interrupt or even reverse fibrosis in individuals with fatty liver disease. I think the key, the key component in in figuring out how to reverse fibrosis, first and foremost, is looking for the cause, identifying the cause of liver disease. So when someone comes to the office and we think there's significant liver disease, it becomes critical to look for potential causes. And that— a lot of that is achieved relatively or excluded relatively quickly with kind of a predetermined panel of blood tests. So to your, to your question of how we improve fibrosis, The answer is identify and treat the underlying cause. Okay? Now, in terms of modifiable factors, okay, if they have obviously weight management, we, we discussed already. Interruption or, or reduction in alcohol consumption is important. And if somebody has cirrhosis, you will have a meaningful discussion about stopping alcohol use altogether. Again, that's another modifiable risk factor. But then beyond that, it's a matter of identifying if there's a viral cause present, if there's an immune-driven cause present, as in autoimmune liver disease. Is there the consideration this could be someone with overload of iron or copper to identify, you know, in terms of describing other liver conditions? Because there are. So there are other less common liver diseases, but the key The uniform goal is identifying the cause of liver disease.

Okay. And can you explain a little bit more about what bile is, where it comes from, and the purpose it serves in the body?

So bile, I said, is produced in the liver. And bile is— the bile system or the biliary system is a production or a system that's unique to the liver, exists only It originates in the liver. So you have to think about the liver as not just this, this factory that is responsible for producing clotting factors for our blood, making proteins, and helping with the metabolic handling of our body, but also a critical component of digestive function because bile serves as the pathway to digestion of fat, as you said, absorption of fat, fat-soluble vitamins. Because, you know, when we eat, everything we take into our intestine is absorbed into our circulation, passes through our liver first. And so the liver identifies and is responsible for processing foods that we eat, including fats, anything that we eat that's foreign. And these substances will be identified and handled in the liver so the, so the biliary system, the bile system, handles fat absorption, handles excretion of toxins that are not excreted through the kidneys, right? Because we handle waste, we get rid of waste in a couple different ways, right? We can pee it out through our kidneys. But if the kidneys can't do that, waste has to be removed another way. And that's often through the biliary system and the stool. So things that circulate within us are often that we don't need, are excreted through bile. Now bile is formed in the liver, in the liver cells, and is passed from the liver cell into something called the canaliculus, which is this little tunnel, if you will, tiny little microscopic pathway in between the liver cells. 'Cause the cell— the liver cells all sort of stack next to each other, but in between them, bile is excreted and passes into tiny little branches. Almost like branches in a tree. Envision the biliary system or the bile system like you would a tree. The main trunk of a tree is the bile duct, which attaches to the gallbladder like a piece of fruit off the tree. So you have this piece of fruit, which is the gallbladder, attaching to a branch, the trunk of the tree, which is the bile duct, which takes— is the repository for all these tiny branches receiving bile from all the bile cells, which is where the leaves would be. Or, well, the liver cells rather, which is where the leaves of the tree would be. So bile is produced and passes down into the bile duct and stored in the gallbladder. The gallbladder stores bile until it's needed. And the gallbladder squeezes in response to a meal. So that's how— and that's the facet of digestion involved using the biliary system. So bile And bile salts have the unique ability to help solubilize or, or help digest fat. 'Cause fat is normally not able to be dissolved into water and most of our body's water. So how do we get fat into our body? Through bile. Because bile can form something called micelles, which solubilizes fats and allows us for for us to absorb fats and fat-soluble vitamins like vitamin D, which is so important now. Everybody talks about vitamin D. We get vitamin D through, through the biliary system. So, so bile serves that purpose. Bile salts, bile acids make their way through the circulation, continue digestive process, and through the small intestine until they reach the end of the small intestine called the ileum. In the ileum, the brain of the small intestine, we have what's called enterohepatic circulation. So those bile substances are reabsorbed into the bloodstream and they make their way back into the liver. It's kinda like a cycle. Some of them leave and go into the large intestine, into the colon. And they actually get further broken down there into other kinds of bile acid. A small amount actually gets excreted in the stool. Most of it is circulated through this enterohepatic circulation. So we recycle all our bile acids. Our bile is sort of a, you know, it's part of this continuously self-feeding factory. The bile acids that enter the colon, interestingly, get further broken down by bacteria in the colon into secondary bile acids. And they actually have an impact on our body as well. Sort of ties in, you know, the microbiome into all this. And you can't, we can't talk about GI, GI illness anymore without somehow involving the microbiome. And it applies in liver disease as well. So bacteria that live in the gut, in the colon, metabolize the bile acids into, into secondary bile acids or or different types of bile acids. And they actually have an impact not just in digestion, but in other physiologic processes in the body. So, the biliary system is part, is a completely independently functioning system separate from the liver itself, the machinery of the liver, and really being critical part of not just digestion in terms of absorption of fat, but also a variety of other processes. And it's also a source where things can go wrong as well. So the same way the liver cells can be damaged with something like hepatitis, viral hepatitis, for example, there can be disorders of bile function, bile production, bile transport that can have an adverse impact on the liver itself as well.

Excuse this brief interruption, but I wanted to remind you that if you've been struggling with IBS, IBD, reflux, gastritis, SIBO, dysbiosis, Candida, diarrhea, constipation, and all that gut health stuff, that's my specialty. So I work with clients not just here in Tucson, Arizona, where I live, but also virtually on video chat. And I offer single appointments as well as a 5-session gut health program for people with tougher gut health issues. Or mental health or autoimmune challenges that go along with that, who likely require testing and longer-term follow-up, as well as 12-week programs for weight loss. If you think that a 5-session or longer course of health coaching might help you meet your health goals, you can set up a free 30-minute breakthrough session with me to talk about what you've been going through, and I'll listen and hear if it sounds like I have something in my toolkit that you haven't already tried and let you know if I think that health coaching would be appropriate for you. You can find a link for that in the show notes, and I hope to hear from you.

And does the bilirubin marker on blood test tell us anything about the bile function?

Yeah, so the, well, so yeah, so the way I like to sort of think about this and, and, and express this to people is think about the bilirubin level as a marker for factory integrity. So, 'cause we talked to Lindsey Parsons about the AST and ALT, right? Those are kind of, and that's indication that maybe this is a factory problem. But factor integrity, liver function, is really often predicted based on the bilirubin level. So the higher the bilirubin, the greater the potential for liver malfunction. That's not always the case, but if a bilirubin level is elevated and there's concerns about liver disease, the context changes. It becomes a bit more urgent. Okay.

Okay. So why might somebody have insufficient bile?

Insufficient bile. Insufficient bile, you mean from the standpoint of inability to excrete bile? From the standpoint of—

No, inability to digest fats or trouble digesting fats. Is that usually because of insufficient or more like clogged bile ducts? No.

Well, okay. So fat malabsorption or fat-soluble vitamin malabsorption can happen in situations of insufficient bile excretion. Okay?

Right.

So, and those conditions are not common, but an example of that would be something like a condition called primary biliary cholangitis, PBC. Used to be called primary biliary cirrhosis, but it's now been renamed primary biliary cholangitis. That's a condition that occurs more commonly in women that results in destruction of the bile ductules. And we mentioned those branches on the tree, that the tiny branches are affected. The ability to produce bile is impacted. And if you can't make bile, if the bile can't be excreted into those little ducts, then over time there's a rise in the bilirubin level in the blood. And if you have insufficient bile production, then you'll have a consequent reduction in fat absorption and also more importantly, fat-soluble vitamin absorption. So individuals with that condition, PBC, that have elevated bilirubin levels can be at risk for fat-soluble vitamin deficiencies. Okay. Okay.

And so then what would cause clogged bile ducts or too thick bile?

Well, so, so bile thickness is impacted mainly by the concentration of bile. So bile that's thick is typically bile that would be more concentrated, say, in the gallbladder. Otherwise bile is the same consistency. But clogged bile ducts can happen because of something that damages, damages the production of bile or movement of bile through the ducts. So that condition, PBC, is one example. There's a condition called primary sclerosing cholangitis, PSC, which is a condition of bile duct damage involving the larger ducts. We mentioned PBC involves the tiny ducts or the ductules. PSC is an inflammatory disease damaging the larger ducts. You can have the inability to have bile flow out of the liver normally in that situation. People develop jaundice. They could be at risk for cirrhosis. And all the complications and consequences associated with cirrhosis from other causes. And is that autoimmune? So PBC and PSC are both felt to be immune-driven conditions. You know, autoimmune— now the way to think about it is autoimmune conditions are never necessarily just autoimmune, but rather combinations of what are multi-hit hypothesis. So it would be somebody who inherits a predisposition to immune disease and then something triggers it to result in the event. In the condition like P— in P— in, and what's interesting about PBC as an example is its predilection for women, 9 to 1 over men. So autoimmune conditions are autoimmune, is an autoimmune tendency with some sort of environmental trigger. Whether it's an infection, dietary, an external agent. There's an interesting theory that, that in PBC, one of the environmental triggers may be something in cosmetics, that there's a— interesting, I just read this— nail polish remover was felt to be a risk factor for PBC. So there may be a substance that's absorbed that triggers the immunity and drives that process. PSC, sclerosing cholangitis, is a condition that coexists very often with another intestinal condition called inflammatory bowel disease. So, immune diseases coexist and the same can exist across body systems.

I had not heard about the nail polish remover. Is it— there's always on some of them, they have a label that says there's no— trying to remember what is not in the nail polish remover. I assume it's the ones that don't have that, that barely work, that are the ones you should be choosing, right?

No, I just happened to come across this because they— I was reading the new guidelines and, you know, we had never— something that we don't tell people about. And it's probably, you know, these are simply based on epidemiologic studies looking at individuals with the condition. So it's hard to, it's hard to counsel people what to do, but I think it just proves that for a lot of these, a lot of these immune-driven conditions, it doesn't necessarily have to be something easily, something as something like an infection. It can be something exogenous.

Yeah. No, I just looked it up. It's acetone. It's the ones you'll see bottles that say no, no acetone. So I assume that must be the bad one.

I don't, I'm not sure. I'm not sure. I think it's hard. It's a hard thing to study because yeah, they're so, you know, the components are so heterogeneous.

Sure. Yeah. Okay. So this is a bit outta left field of the topic of liver disease and bile, but I do see clients all the time who get negative biopsies for H. pylori during an endoscopy, but they're clearly symptomatic for it. They have reflux or they have constipation. And then I run a, a GI MAP on them, which is a stool test, and, and they show high levels on this PCR test. So I'm curious why there isn't more testing for H. pylori beyond biopsies by gastroenterologists.

Well, you mean using other methods to, to diagnose it?

Yeah, like urea breath tests or stool, stool antigens. Well, I do.

I think that the answer to your question is it is, first of all, we try to be efficient. So if we're doing an endoscopy on somebody who has symptoms and it's appropriate to have an endoscopy done, then we will certainly do a biopsy for H. pylori. And there's, there's a couple of important things to keep in mind. First of all, a biopsy should be done from two spots in the stomach to confirm it, because you can have a biopsy be positive in one area and negative in the other. So we will commonly do a biopsy from what's called the antrum, which is lower stomach, which is where H. pylori likes to be, but also do one from the body of the stomach, because often one would be positive and the other would be negative. The other This is also really important, is that acid suppression, particularly with something called a PPI or proton pump inhibitor, which are these drugs that would include Prilosec, Nexium, Prevacid, acid suppression impacts the environment for H. pylori propagation or the milieu. The, the, the bug likes acid. So if you suppress acidity in the stomach, you will reduce the, the ability to identify H. pylori. So if we suspect H. pylori and we don't see it on a biopsy, that's often one of the things that we'll consider. Did we miss it because either sampling or because they got their biopsies done while taking acid suppression therapy? Keep in mind that a breath test cannot be done if somebody's been using a PPI or an acid suppression using a— using that proton pump inhibitor. So, so to go back to your initial query, I would say if we suspect H. pylori, we should look for it in an efficient way. And a biopsy is very efficient if they need an endoscopy. If an endoscopy is not necessary, a breath test or a stool antigen are equally effective. In di— making the diagnosis. Okay.

So yeah, and obviously if you're having a PCR test, you're just looking at H. pylori anywhere in the intestines. So it's only problematic when it's overgrown in the stomach or, and had, or, and/or has virulence factors?

Well, yeah, we don't typically do a PCR test for H. pylori, so.

Right. No, that's a test I see a lot though for, for my clients. Yeah. So that's why I'm mentioning it.

So. So H. pylori is a bacteria that's found in the stomach. It's, that's the milieu, that's the, that's its area of identification.

So it's not hanging out in other parts of the intestine. If it's, if it's high, it's coming from the stomach.

Well, if, well, if it, sorry, if we identify H. pylori, that we, it's, it's by definition an H. pylori gastritis. So you can identify H. pylori in the stool. You can look for the antigen in the stool. But that's the result of bacteria that was shed in the stool from the stomach. Right. I hope I, that was clear. Yeah. Okay.

So yeah, basically that, that H. pylori lives in the stomach. That's the part of the— Yeah. It's digestive tract that it prefers.

Correct. H. pylori is the most common, it's the most common pathogenic agent worldwide. Half the, half the world has H. pylori. You know, it's— that's a whole other sort of— I know we got off topic, you know, to liver, but it's important nonetheless and probably a subject for a whole other discussion. But H. pylori is a worldwide epidemiologic issue responsible for probably the majority, the vast majority of, you know, the all ulcer disease involving the duodenum, peptic ulcer disease of the duodenum, small intestine, responsible for the majority of ulcer diseases involving the stomach. And it's an established risk factor for cancer of the stomach, something called MALT, which is a lymphoid tumor of the stomach, as well as being responsible for other health conditions, the link of which many are clear, other potential health conditions. So it's an issue. It's an issue. Okay.

Well, thank you for that. We're— we've run out of time, so I'll have to do a different show on H. pylori entirely. Which I actually haven't focused a single episode on. So that's probably a good, good next one.

Thank you so much for coming on.

Any final words before, before we close out?

No, I, I thank you. You know, I, I think that, I think the important thing is that, you know, the liver's kind of like this forgotten, it's kind of been lost in the mire of, of, of intestinal conditions. And I'm glad to hear that it's gained its rightful place in the discussion. And I, I appreciate this opportunity to talk a little bit about it. Great.

Well, I appreciate you coming on. Thanks so much.

Thanks, Lindsey. Have a good day.

If you'd like to find Dr. Nakias, I'll put a link in the show notes to his website and his practice in River Edge, New Jersey. And if you're a longtime listener or getting a lot of useful info from the podcast, please consider becoming a regular supporter on Patreon. And if you'd like to connect with me online, you can follow my High Desert Health Facebook page, join my Gut Healing Facebook group, or join my newsletter list at highdeserthealthcoaching.com, as well as Twitter Instagram and Pinterest. Links for all of those are in the show notes. Thanks for joining me today, and here's wishing you all the perfect stool.