Adapted from episode 97 of The Perfect Stool podcast and edited for readability with George Nikias, MD, Gastroenterologist practicing with Hackensack Gastroenterology Associates.
Lindsey:
So, I understand liver disease is your specialty. Can you give an overview of the things that go wrong with the liver and what the signs and symptoms are?
Dr. George Nikias:
Sure. Liver disease is a subspecialty of gastroenterology, and it’s a growing one. And the patients will see that liver disease will range from a person who feels well that has abnormal blood tests related to the liver, perhaps identified by their primary doctor, or primary health care 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. 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 very conditions that affect the liver.
Lindsey:
Yes, let’s talk about those different conditions and how they come about.
Dr. George Nikias:
Why don’t we work from a common everyday scenario in the clinic that we often deal with, and we can expand from there? Very often, we’ll see individuals that come to the office or the clinic with no complaints other than being told by their primary health care provider that they have abnormalities in their liver tests, and often they will seek further evaluation on the computer and learn of potential causes. At the same time, this can also be a point of alarm for people with fears that perhaps their liver is failing or not functioning. But very often, it’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 health care 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 is now being described, non-alcoholic fatty liver disease, which has now evolved into 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 not just to liver disease, but overall health and longevity.
Lindsey:
And how does this come about?
Dr. George Nikias:
Well, the common scenario, or the common condition that exists with fatty livers, typically, is a weight above normal, or elevated body mass index, as we call them. The common theme seems to be central obesity, or abdominal fat, which we’ve now learned isn’t simply a storage platform per calorie, but 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. That being said, individuals who are heavy are at risk for fatty liver disease. 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. Fatty liver can be the prequel, if you will, to the development of metabolic syndrome, diabetes, and potentially systemic changes in the body, or complications in the body occurring from that physiologic change. So the evolution is from individuals developing fatty liver disease, if not risk for diabetes, metabolic syndrome, high blood pressure, associated high lipids, and complications from that, particularly cardiovascular and other vascular diseases.
Lindsey:
Will you typically see blood sugar or fasting glucose or A1C rise before you see the liver enzymes rise? Because I’ve seen a lot of that without elevated liver enzymes.
Dr. George Nikias:
I think that’s the important caveat. 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 an umbrella that covers everyone’s 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 view it is, it’s this iceberg or this all encompassing term, fatty liver, and then within it, a subset of individuals with true risk for significant liver disease. And so, to go back to answer your questions, you can have normal liver tests and have fatty liver. Then the bigger question is, 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. That’s where it gets a little bit tricky.
Lindsey:
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. I’m wondering if they play out differently, other than the cause, and if the things that can mitigate or reverse the conditions are any different other than obviously, one requires stopping drinking, and the other one, probably changing your diet?
Dr. George Nikias:
Yeah, I think that it’s a good question. A lot of the problem with fatty liver in general is that we don’t have good treatments. And so it behooves us, if someone is over-using alcohol, to counsel them about reduction, if not elimination of alcohol. If they have fatty liver in general, or risk factors for 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 that has maybe casual alcohol use, but also has risk factors for non-alcoholic fatty liver and has abnormal liver tests. How do we counsel them to make changes to determine that we’re having an effect on the other condition? Like you said, Lindsey, stopping alcohol or reducing alcohol is one very effective intervention for alcoholic fatty liver, but how do we counsel someone regarding modest alcohol use if they have fatty liver, incidentally? So this becomes a tricky thing to work through.
Lindsey:
Yeah. So what do you tell patients about reversing fatty liver? Because 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 adopted a more healthy attitude that their health is what their goal is, not their weight. So I’m just curious, when people have disordered eating, it’s so complex.
Dr. George Nikias:
I think first of all, the key is to is to have them set goals that are realistic. What we do when we see them first and tell them they have this condition, first of all, we reassure them that the vast majority of people that have fatty liver will not die of liver disease. However, this is important, what we tell them is that you are at risk for vascular complications. So the goal here is, as you said, total body health and achieving that. If you look at this in a two-pronged way, if we look at the evaluation of liver disease, there are measures we take to stratify risk, to identify if they are at risk for significant liver disease, and we can do that very simply. From looking at the 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 the 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 transported through the liver. A harder liver, a harder substance transports sound quicker. The speed of which the echo of that sound is transferred through the liver is measured. If the speed is faster, then the liver is going to be harder than the fibrosis index, or the E score is higher on that FibroScan test. 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 goal, is giving them tangible, actionable goals to shoot for in terms of weight loss, because the vast majority of these individuals have above normal body weight. So the numbers we’ll use 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 that the goal here is not dropping huge amounts of weight in a short period of time, but rather, aiming to lose 7% of your body weight, which is, I think, realistically achievable for many people. 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 a tangible goal, and then the extension of that is, we’ll ask what diet we should do. And there’s been some work in this. There’s still, I think, a lack of clarity as to what the ideal diet is for fatty liver, but data seems to suggest that a Mediterranean diet really stands forward 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 individuals.
Lindsey:
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. So that’s just unrealistic as a long term plan, but an easy way of losing a lot of weight fast.
Dr. George Nikias:
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 intervention, which is not pragmatic. And we know that any short-term intervention is bound to fail. So what I say is, look, just don’t think about this as something you need to do for three months, or six months, or even a year. Think about it as something you’re going to do permanently, so make it achievable, change is slight. And the other big thing is activity and encourage them just to go out. If you don’t walk, just walk five minutes the first day and walk 10 minutes the next week after that. So my view is that, what I want to espouse is lifestyle changes that are permanent, but in order to be permanent, it has 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 should view the condition as long as it’s not going to impact them anytime soon. 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.
Lindsey:
Can you explain a little bit the different terms and stages of liver disease? So you have fatty liver and I know there’s cirrhosis, fibrosis: How does that progress?
Dr. George Nikias:
Sure. Let’s look at the condition of fatty liver, because fatty liver is sort of all encompassing. 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’s 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 used to define non-alcoholic steatohepatitis. In that case, that represents about 25% of the total group of individuals with fatty liver. In that case, there is fatty change associated with inflammation. From within that group, there is the highest risk of fibrosis, which is the term used to define scarring of the liver. Then, fibrosis is graded along a well defined staging score that moves from stage one to stage four, stage one being minimal fibrosis and stage four being cirrhosis. So cirrhosis, and all the pejorative connotations associated with it, really is simply a way to define the end stages of a defined scarring pattern across all liver disease, 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.
Lindsey:
Is cirrhosis 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 spreads?
Dr. George Nikias:
No. Cirrhosis is something that impacts the whole liver. And that’s often one of the big discussions when somebody comes, and they need liver surgery. They’lI say, I have this problem, can we just cut the liver out, because I’ve heard that the liver can just grow back? That’s like the mythological story of the guy who 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 as it would grow back. That happens with a healthy liver. So if you have a healthy liver, and you lose half of it because of surgery, for example, it will grow back to reoccupy the space that had existed before. A liver that’s cirrhotic doesn’t have that same capacity. That’s because cirrhosis is a uniform scarring process across the whole liver.
Lindsey:
And fibrosis too, that’s throughout the whole liver?
Dr. George Nikias:
So yeah, so fibrosis is, think about fibrosis as this very spidery 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 have now encircled the liver. And that nodule appearance of the liver that we associate with cirrhosis is expansion and densening of the fibrosis to become cirrhosis.
Lindsey:
Okay, and can you tell about the stage of liver disease from the ALT and the AST markers on the blood test?
Dr. George Nikias:
Now, what the ALT and AST markers do is tell us whether there’s potentially a liver disease or liver condition at play. So these tests are, if you will, screening tests for a 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 they just confuse you, there’s a disconnect there. If an individual comes to the office and says I’ve been told I have cirrhosis, but my liver tests were always okay or maybe just a few points off, how could this happen? It’s because it’s not as straightforward as a link between the level of elevation of those tests and risk.
Lindsey:
Are those tests testing how much the liver is currently being damaged as opposed to how much it has progressively been damaged?
Dr. George Nikias:
Right, that’s a good question. So intuitively, you think that a higher elevation in those tests corresponds to more liver damage, and that can be the case. Let’s say somebody has hepatitis because they ate contaminated food and developed hepatitis A, for example. Well, those liver tests can rise dramatically. Very high. Let’s say normal ALT for healthy adults is between 25 and 30. For someone with viral hepatitis that number can rise as high as 1000, 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 their 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 levels can actually be normal or minimally elevated. So we get insights into the cause of liver disease by the pattern of elevation and the degree of elevation. But it doesn’t always give us insight into the severity.
Lindsey:
Well, obviously, it sounds like it’s not something that’s consistent across people, but I’m just curious 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?
Dr. George Nikias:
Well, the diagnosis of liver failure isn’t predicted by the AST or ALT. 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, it’s part of that metabolic profile that we talked a little bit about, that chemistry panel. So the bilirubin can be elevated, which gives us insights into the way the liver functions normally. There is also albumin, 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 ALT can be normal or near normal, and someone can have liver failure.
Lindsey:
So with transplants, the donor base, I’m guessing, is probably somewhat larger if you can cut off a piece of a liver and still have it regrow. So if somebody gives up a piece of their liver, they might still be perfectly fine?
Dr. George Nikias:
Well, yeah, 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 works from that very virtue, which is that 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 tells you that it will grow over time.
When you do a liver transplant, I assume you completely remove the diseased one and you put in the new one?
Yeah, with liver transplants, the whole organ is removed and replaced with a new liver. That’s because, the diseased organ, the complications of liver disease, are many fold besides just not functioning in terms of the metabolic demands of the body. One of the other big problems of the liver is the problem with high pressure in the main vessel and main vein that feeds the liver called the portal vein. One of the complications of cirrhosis is high pressure in that vein. So, in order to correct that, the native organ needs to be taken out, because you’d think if you have a liver 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.
Lindsey:
Okay, so is reversal of fibrosis or cirrhosis of the liver possible? Because I actually just published an episode, Episode 89, with Dr. Barrie Tan, who did a study on tocotrienols* (available in my Fullscript dispensary), 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 in your experience fibrosis scores can go down and if you’ve used the tocotrienols?
Dr. George Nikias:
It’s such a great question. It’s actually an area of very intense study, not just in fatty liver, but across across liver disease in general, because cirrhosis represents, as we’ve said, the end stage of the scarring or fibrosis process. If we can interrupt or reverse fibrosis, then we can essentially eliminate the risk of cirrhosis and the complications of cirrhosis. So is fibrosis regression possible? The answer is yes. And this has been shown across multiple liver diseases, including hepatitis B, where patients that have cirrhosis will have the cirrhosis regressed. The thought was always that scar tissue is permanent. Like if you ever cut your arm and a wound forms and it’s fine, but that’s fibrosis, right? It’s a response to injury. Well, the perception was always that fibrosis in the liver, that response to injury, was permanent. 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. Again, we talked 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 the 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, where you have control of the agent that’s driving inflammation, will still not allow the cirrhosis to reverse. But, and this is actually really interesting, if you have somebody with hepatitis B and liver failure, for example, and you put them on treatment, if they respond to their treatment and the liver failure is controlled, there can eventually be liver healing. There’s other conditions for example, like autoimmune liver disease, which is a hepatitis that can look just like a virus but it’s actually our own body damaging our liver. Autoimmune liver disease, if controlled, fibrosis there regresses and shrinks away. So yes, fibrosis is a dynamic process, and it’s reversible. Cirrhosis, the end stage of fibrosis, is also dynamic. So early cirrhosis, right, that spidery scar tissue, not too dense, reversible, shrinks away. When it is 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 poses the question of when do you go over that cliff? When is one of the changes irreversible or permanent? 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.
Lindsey:
What causes gallbladders to stop functioning properly and create stones?
Dr. George Nikias:
Well, gallbladder stones are the result of a change in the solubility of the contents in bile. 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 and the 5% is comprised of a variety of substances. 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, as well as other metabolic processes. Bile is composed of bile salts, cholesterols, phospholipids, proteins, potassium, sodium, and things like that. And this all exists in the solution. The theory is that for a variety of reasons, the solution falls out of its stable state, and things begin to precipitate out. It’s those precipitants for example, cholesterol, or other components of bile, that begin to lead to the production of stones. And stones, which can often exist without symptoms, can rest in the gallbladder where they just 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 can become stuck in the neck of the gallbladder. This is the source of the pain. The pressure in the gallbladder itself causes biliary type pain or gallbladder pain.
Lindsey:
And where will you feel that?
Dr. George Nikias:
The most common place is actually underneath the breastbone but often radiating to the right-upper abdominal area of the right flank. So often, it will be 30 to 45 minutes after a fatty meal. People can often have symptoms at night, which is kind of curious because you’re not eating then. People often complain of similar kinds of pain waking them from sleep. Again gallbladder pain is a sign of not so much a 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, that’s what is called cholecystitis. That’s the consequence of that issue.
Lindsey:
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?
Dr. George Nikias:
Well, that’s the tricky thing, 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, or risk of complications into a straightforward operation that now is almost done on an outpatient basis. People will come in in the morning and go home in the afternoon with a gallbladder gone. So laparoscopic surgery simplified the intervention for gallbladder problems, but there are people who will ask about non-operative interventions. We’ll talk to them and we’ll say, look, weight loss can sometimes facilitate gallstone dissolution. Interestingly, paradoxically, rapid weight loss results in gallstone formation. So they’re looking to lose weight, which goes back to this whole idea that there’s no quick fix for anything. It should all be gradual, and sort of reasonable. But weight loss can help with gallstone dissolution. The other thing I will tell them 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 that has been around for a long time that is 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 from their gallbladder.
Lindsey:
What about diet changes or eating things that help thin the bile?
Dr. George Nikias:
There’s no diet specifically that will change bile composition. Urso, that supplement, will change the composition of bile. As far as diet, typically fatty food will trigger gallbladder attacks; we will counsel people to perhaps have a lower fat diet. But it’s not a durable fix, if you will.
Lindsey:
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 and/or non traditional treatments can you point to?
Dr. George Nikias:
I think that’s an important question. So we talked a little bit about the common one, which is fatty liver. And the way to reverse fibrosis by the liver is again aiming for weight loss. Weight loss does have the ability to interrupt or even reverse fibrosis in individuals with fatty liver disease. I think the key component 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 see significant liver disease, it becomes critical to look for potential causes and a lot of that is achieved or excluded relatively quickly. It’s a predetermined panel of blood tests. So to your question of how we improve fibrosis, the answer is identify and treat the underlying cause. Now, in terms of modifiable factors, there obviously, is weight management, which we discussed already, interruption or reduction in alcohol consumption is important. If somebody has cirrhosis, we will have a meaningful discussion about stopping alcohol use altogether. And, again, that’s another modifiable risk factor. But then beyond that, it’s a matter of identifying if there is a viral cause present, if there’s an immune driven cause present as in autoimmune liver disease. Is there consideration this could be someone with overload of iron, or copper, 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.
Lindsey:
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.
Dr. George Nikias:
So bile, I said, is produced in the liver. The biliary system is a system that’s unique to the liver, it originates in the liver. So you have to think about the liver as not just 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 when we eat, everything we take into our intestines is absorbed into our circulation, it passes it 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 biliary system, the bile system, handles fat absorption, handles excretion of toxins that are not excreted through the kidneys. So we get rid of waste in a couple of 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 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 tiny, little microscopic pathway in between the liver cells, because the liver cells are stacked next to each other. But in between them, bile is excreted and passes it 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 is the repository for all these tiny branches, receiving bile from all the liver cells, which is where the leaves of the tree would be. So bile is produced and passes down into the bile duct, and is stored in the gallbladder. The gallbladder stores bile until it’s needed. The gallbladder squeezes in response to a meal. So that’s the facet of digestion involved using the biliary system. So bile and bile salts have the unique ability to help solubilize or help digest fat, because fat is normally not able to be dissolved into water, and most of our body is water. So how do we get fat into our body through bile? Because bile can form something called micelles, which solubilizes fat, and allows for us to absorb fat and fat soluble vitamins like vitamin D, which is so important. Now everyone talks about vitamin D, we get vitamin D through the biliary system. So bile serves that purpose. Bile salts and bile acids, make their way through the circulation, continued 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 a cycle. Some of them leave and go into the large intestine, the colon and they actually get further broken down there into other kinds of bile acids. A small amount actually gets excreted into stool, most of it is circulated through this enterohepatic circulation. So we recycle all our bile acids, our bile is 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, which ties into the microbiome and all this. You can’t talk about 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, different types of bile acids, and they actually have an impact not just on digestion, but other physiologic processes in the body. So the biliary system, is a completely independently functioning system, separate from the liver itself. The machinery of the liver is really the 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.
Lindsey:
And does the bilirubin marker on a blood test tell us anything about the bile function?
Dr. George Nikias:
Yeah. So the way I like to think about this and express this to people is to think about the bilirubin level as a marker for factory integrity. Because we talked, Lindsey, about the AST and ALT; those are an indication that maybe there’s a factory problem. But factory 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, due to context changes, it becomes a bit more urgent.
Lindsey:
Okay. So why might somebody have insufficient bile?
Dr. George Nikias:
Insufficient bile from the standpoint of inability to excrete bile?
Lindsey:
Inability to digest fats or trouble digesting fats? Is that usually because of insufficient bile or more like clogged bile ducts?
Dr. George Nikias:
So fat soluble vitamin malabsorption can happen in situations of insufficient bile excretion. And those conditions are not common. But an example of that would be something like a condition called primary billary cholangitis, PBC. It 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 ductuals. We mentioned those branches on the tree; 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 that 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, and so then what would cause clogged bile ducts or too thick bile?
Bile thickness is impacted mainly by the concentration of bile. So bile that’s thick, is typically bile that would be more concentrated in the gallbladder. Otherwise, bile is the same consistency, but clog bile ducts can happen because of something that 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 ductuals. PSC is an inflammatory disease damaging the larger ducts. You can have the inability to have bile flow. At the liver normally in that situation, you would develop jaundice, you could be at risk for cirrhosis, and all the complications and consequences because of cirrhosis and other causes.
Lindsey:
And is that autoimmune?
Dr. George Nikias:
PBC and PSC are both felt to be immune-driven conditions. The way to think about it is that autoimmune conditions are never necessarily just autoimmune, but rather combinations of a 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. And what’s interesting about PBC as an example, is its predilection for women nine to one over men. So autoimmune conditions is an autoimmune tendency, with some sort of environmental trigger, whether it’s an infection, dietary or an external agent. There’s an interesting theory that in PBC, one of the environmental triggers might be something in cosmetics, that there’s a link. It’s interesting, I just read this, nail polish remover was thought to be a risk factor for PBC. So there may be a substance that’s absorbed that triggers the immunity forward and drives that process. PSC 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.
Lindsey:
I had not heard about the nail polish remover. On some of them they have a label that says there’s no – I’m 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.
Dr. George Nikias:
I just happened to come across this because they I was reading the new guidelines. And it’s something that we don’t tell people about, and these are simply based on epidemiologic studies looking at individuals with the condition. So 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 like an infection. It could be something exogenous.
Lindsey:
Yeah, I just looked it up, it’s acetone. It’s the ones you’ll see bottles that say “no acetone”, so I assume that must be the bad thing.
Dr. George Nikias:
I’m not sure. I’m not sure. But I think it’s a hard thing to study. Because there’s so many other components, it’s so heterogeneous.
Lindsey:
Sure. So this is a bit out of 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 GI Map on them, which is a stool test 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.
Dr. George Nikias:
Well, you mean using other methods to . . .
Lindsey:
Urea breath tests or stool antigens?
Dr. George Nikias:
The answer to your question 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 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 take a biopsy from what’s called the antrum, which is the lower stomach, which is where H. pylori likes to be, but also do it from the body of the stomach, because often one would be positive and one would be negative. The other thing that’s also really important is that acid suppression, particularly with something called a PPI, or proton pump inhibitor, which is of these drugs that would include Prilosec, Nexium, Prevacid. Acid suppression impacts the environment for H. pylori propagation or the milieu. The bug likes acid, so if you suppress acidity in the stomach, you will reduce 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 breath test cannot be done if someone has been using a PPI or an acid suppression using a proton pump inhibitor. 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. And if an endoscopy is not necessary, a breath test or stool antigen are equally effective in making the diagnosis.
Lindsey:
Okay, and obviously if you’re having a PCR test, you’re just looking at H. pylori anywhere in the intestine. So is it only problematic when it’s overgrown in the stomach and/or has virulence factors?
Dr. George Nikias:
Well, we don’t typically do a PCR test for H. pylori.
Lindsey:
Right, that’s a test I use a lot though for my clients. So that’s why I’m mentioning it.
Dr. George Nikias:
So H. pylori is a bacteria that’s found in the stomach. That’s the milieu. That’s its area of identification.
Lindsey:
It’s not hanging out in other parts of the intestine? If it’s high, it’s coming from the stomach?
Dr. George Nikias:
So if we identify H. pylori, 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 a bacteria that was shed in the stool from the stomach. I hope that was clear.
Lindsey:
Yeah. Okay. So yeah, basically, H. pylori lives in the stomach, that’s the part of the digestive tract that it prefers.
Dr. George Nikias:
H. pylori is the most common pathogenic agent worldwide. Half the world has H. pylori. Yeah, that’s a whole other . . . I know, we got off topic about the liver, but it’s important nonetheless, and probably a subject for a whole other discussion. H. pylori is a worldwide epidemiologic issue, responsible for the vast majority of all ulcer disease involving the duodenum, peptic ulcer disease of the duodenum, the small intestine, responsible for the majority of ulcer diseases involving the stomach. And, it’s an established risk factor for cancer of the stomach. It’s 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 aren’t clear and other potential health conditions. So it’s an issue.
Lindsey:
Okay. Well thank you for that. We’re 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 next one. Thank you so much for coming on. Any final words before we close out?
Dr. George Nikias:
No, thank you. I think that the important thing is that, the liver has been lost in the mire of intestinal conditions. And I’m glad to hear that it’s getting its rightful place in the discussion, and I appreciate the opportunity to talk a little bit about it.
If you’re struggling with bloating, constipation, diarrhea, soft stool, acid reflux, IBS, IBD or any type of chronic disease, etc. and want to get to the bottom of it, that’s what I help my clients with. You’re welcome to set up a free, 30-minute breakthrough session with me (Lindsey). We’ll talk about what you’ve been going through and I’ll tell you about my 3- and 5- appointment health coaching programs in which I recommend lab tests, educate you on what the results mean and the protocols used by doctors to fix the problems revealed. Or if you’re ready to jump in right away or can just afford one appointment at a time, you can set up an 1-hour consultation with me.
