Physician/Researcher Views
Article by Craig Lammert, AIHA
The immune system is a complex network of different cell types, their secreted substances, and downstream targets. Cytokines are an integral part of this system; these are small proteins that are secreted by various cell types to impact others. These cytokines can have many downstream actions in the immune system, including immune cell activation, responsiveness to certain stimuli, or even maturation of that cell in its’ life cycle. Thus it is easy to see that cytokines may be very important in an over reactive immune system in autoimmune hepatitis (AIH). Understanding the types of cytokines that are upregulated in autoimmune disease may give us a better view of ways to treat the disease and or act as “biomarkers” to assist in diagnosis, monitoring treatment, or predicting outcomes.
A recent Russian study (published this month) recently has reported the findings of various cytokine levels in healthy controls, autoimmune hepatitis, and autoimmune hepatitis with features of a variant syndrome (PSC or PBC). This is the first time this has been done. The aim of the study was to reveal the differences in the serum cytokine levels between these patient groups in order to further assess specific clinical features of autoimmune liver disease.
This was a small group snapshot of cytokines, as only 32 patients with AIH, 28 patients with AIH-variant syndrome, and 21 healthy controls were includrf. The authors found that patients with any type of autoimmune liver disease (AIH and AIH-variant syndrome) had significantly higher levels of IL-6 (Interleukin), IL-8, and TNF-α. They also observed in statistical modeling that an increase of IL-8 serum level by 1 pg/mL increased the chance for autoimmune liver disease almost 50 times. Also, high IL-8 serum levels were strongly related to clinical parameters – higher values related to higher liver tests and markers of inflammation.
What does this mean? First, the study results may be the start of further understanding some of the immune signaling that is disrupted in these diseases. IL-8 could be a possible future diagnostic and prognostic tool if the author’s findings are replicated. Secondly, these studies may pinpoint that anti-IL8 therapies could be included in future therapeutic targets in autoimmune liver diseases. Thirdly, and probably most importantly, this is a small study. These types of investigations will be better to be done on a large scale approach, and linked to other genomic data so that a more complete “inflammatory” profile can be interrogated.
Despite these types of studies are not perfect, it does show progress and research interest in AIH. This is something we can all get behind.
The immune system is a complex network of different cell types, their secreted substances, and downstream targets. Cytokines are an integral part of this system; these are small proteins that are secreted by various cell types to impact others. These cytokines can have many downstream actions in the immune system, including immune cell activation, responsiveness to certain stimuli, or even maturation of that cell in its’ life cycle. Thus it is easy to see that cytokines may be very important in an over reactive immune system in autoimmune hepatitis (AIH). Understanding the types of cytokines that are upregulated in autoimmune disease may give us a better view of ways to treat the disease and or act as “biomarkers” to assist in diagnosis, monitoring treatment, or predicting outcomes.
A recent Russian study (published this month) recently has reported the findings of various cytokine levels in healthy controls, autoimmune hepatitis, and autoimmune hepatitis with features of a variant syndrome (PSC or PBC). This is the first time this has been done. The aim of the study was to reveal the differences in the serum cytokine levels between these patient groups in order to further assess specific clinical features of autoimmune liver disease.
This was a small group snapshot of cytokines, as only 32 patients with AIH, 28 patients with AIH-variant syndrome, and 21 healthy controls were includrf. The authors found that patients with any type of autoimmune liver disease (AIH and AIH-variant syndrome) had significantly higher levels of IL-6 (Interleukin), IL-8, and TNF-α. They also observed in statistical modeling that an increase of IL-8 serum level by 1 pg/mL increased the chance for autoimmune liver disease almost 50 times. Also, high IL-8 serum levels were strongly related to clinical parameters – higher values related to higher liver tests and markers of inflammation.
What does this mean? First, the study results may be the start of further understanding some of the immune signaling that is disrupted in these diseases. IL-8 could be a possible future diagnostic and prognostic tool if the author’s findings are replicated. Secondly, these studies may pinpoint that anti-IL8 therapies could be included in future therapeutic targets in autoimmune liver diseases. Thirdly, and probably most importantly, this is a small study. These types of investigations will be better to be done on a large scale approach, and linked to other genomic data so that a more complete “inflammatory” profile can be interrogated.
Despite these types of studies are not perfect, it does show progress and research interest in AIH. This is something we can all get behind.
SOCIAL SUPPORT and STIGMA - Jessica Naftaly
Jessica Naftaly is a PhD Clinical Psychology graduate student studying health psychology and the psychosocial aspects (stress, coping, medication adherence, social support, etc) of chronic illnesses. A background in psychology coupled with a personal experience with AIH gives Jessica a unique perspective in this much understudied facet of AIH.
In addition to the physical symptoms autoimmune hepatitis (AIH) patients manage daily, many do not know that it also important to take care of one’s mental health. It is common for patients with chronic illnesses to experience symptoms of mental illnesses such as depression and anxiety. (Chapman, Perry, & Strine, 2005). Not only should patients be mindful of their mental health, but also ways to improve their mental health. One way to maintain excellent mental health is by having a good support system.
Patients with chronic medical conditions tend to have better health outcomes when they a solid social support system. However, having a stigmatized illness like AIH can make talking with friends and family members about AIH challenging. Due to a lack of common knowledge about the various types of liver diseases, people sometimes assume that ALL liver diseases are contracted through unprotected sex, sharing needles, and drinking too much alcohol. These aspects are part of a stigma of all liver diseases. However, like AIH there are plenty of other liver diseases (fatty liver disease) that do not develop this way.
In fact, experiencing some type of perceived stigma is pretty common in patients with liver diseases. In a research study on patients with various liver disease and cirrhosis, 89% reported experiencing stigma about their liver disease and 75% indicated that they do not talk with others about their liver disease (Vaughn-Sandler, Sherman, Aronsohn, & Volk, 2013). You may think “what’s wrong with experiencing stigma?” The study also found that patients who experienced more stigma were more likely to be depressed, less likely to have social support, less likely to go to the doctor, and were less likely to take their medication. Patients with high amounts of perceived stigma overall had a lower quality of life (Vaughn-Sandler, Sherman, Aronsohn, & Volk, 2013). I’m not going to lie to you; there will always probably be some amount of stigma that the public voices about liver diseases. There are however, some things that we as patients, can do to cope with the stigma and be able to talk to friends about AIH.
Many patients find it helpful to educate themselves about AIH so that when people ask them questions, they know how to answer and better explain AIH. Additionally, patients who are knowledgeable about their disease tend to feel empowered and more confident when talking about AIH. It can be useful to develop an “elevator speech” in which you are able to explain what AIH is in a couple of sentences. For example, normally our immune systems are pretty good at attacking only foreign items, however with autoimmune hepatitis, our bodies attack the liver (a healthy organ) creating inflammation of the liver. Patients cannot control whether the body attacks itself or not. There are multiple components that contribute to the development of the disease like genetics, environment, medications, etc. We don’t know exactly how AIH forms, however we do know that AIH is not contagious. Sometimes taking on the educator role not only helps the public become more informed about AIH, but also empowers yourself to tell others about your AIH experience.
No different than having friends that you can tell some things to compared to other friends; choosing which friends and family members to talk about your AIH with may be viewed the same way. We all have those friends that we know we can tell our deepest secrets too and others who aren’t the greatest at listening to our concerns. There’s nothing wrong with picking and choosing who you talk to about AIH. You don’t need to tell the whole world about AIH (but feel free to), but talking with others about AIH and having that social support can lead to better outcomes. It’s also important to develop social support from others that also have AIH. It’s a great feeling talking with someone else that also has AIH and a mutual understanding what each of you are going through. Despite the AIH community being small, there are plenty of patients on social media via the Autoimmune Hepatitis Research Network and the Autoimmune Hepatitis Association. Post a question on there every once in a while. You’ll be surprised by the amount of patients that are willing to help! Plus your AIH friends understand what it’s like to experience stigma with AIH.
Jessica Naftaly is a PhD Clinical Psychology graduate student studying health psychology and the psychosocial aspects (stress, coping, medication adherence, social support, etc) of chronic illnesses. A background in psychology coupled with a personal experience with AIH gives Jessica a unique perspective in this much understudied facet of AIH.
In addition to the physical symptoms autoimmune hepatitis (AIH) patients manage daily, many do not know that it also important to take care of one’s mental health. It is common for patients with chronic illnesses to experience symptoms of mental illnesses such as depression and anxiety. (Chapman, Perry, & Strine, 2005). Not only should patients be mindful of their mental health, but also ways to improve their mental health. One way to maintain excellent mental health is by having a good support system.
Patients with chronic medical conditions tend to have better health outcomes when they a solid social support system. However, having a stigmatized illness like AIH can make talking with friends and family members about AIH challenging. Due to a lack of common knowledge about the various types of liver diseases, people sometimes assume that ALL liver diseases are contracted through unprotected sex, sharing needles, and drinking too much alcohol. These aspects are part of a stigma of all liver diseases. However, like AIH there are plenty of other liver diseases (fatty liver disease) that do not develop this way.
In fact, experiencing some type of perceived stigma is pretty common in patients with liver diseases. In a research study on patients with various liver disease and cirrhosis, 89% reported experiencing stigma about their liver disease and 75% indicated that they do not talk with others about their liver disease (Vaughn-Sandler, Sherman, Aronsohn, & Volk, 2013). You may think “what’s wrong with experiencing stigma?” The study also found that patients who experienced more stigma were more likely to be depressed, less likely to have social support, less likely to go to the doctor, and were less likely to take their medication. Patients with high amounts of perceived stigma overall had a lower quality of life (Vaughn-Sandler, Sherman, Aronsohn, & Volk, 2013). I’m not going to lie to you; there will always probably be some amount of stigma that the public voices about liver diseases. There are however, some things that we as patients, can do to cope with the stigma and be able to talk to friends about AIH.
Many patients find it helpful to educate themselves about AIH so that when people ask them questions, they know how to answer and better explain AIH. Additionally, patients who are knowledgeable about their disease tend to feel empowered and more confident when talking about AIH. It can be useful to develop an “elevator speech” in which you are able to explain what AIH is in a couple of sentences. For example, normally our immune systems are pretty good at attacking only foreign items, however with autoimmune hepatitis, our bodies attack the liver (a healthy organ) creating inflammation of the liver. Patients cannot control whether the body attacks itself or not. There are multiple components that contribute to the development of the disease like genetics, environment, medications, etc. We don’t know exactly how AIH forms, however we do know that AIH is not contagious. Sometimes taking on the educator role not only helps the public become more informed about AIH, but also empowers yourself to tell others about your AIH experience.
No different than having friends that you can tell some things to compared to other friends; choosing which friends and family members to talk about your AIH with may be viewed the same way. We all have those friends that we know we can tell our deepest secrets too and others who aren’t the greatest at listening to our concerns. There’s nothing wrong with picking and choosing who you talk to about AIH. You don’t need to tell the whole world about AIH (but feel free to), but talking with others about AIH and having that social support can lead to better outcomes. It’s also important to develop social support from others that also have AIH. It’s a great feeling talking with someone else that also has AIH and a mutual understanding what each of you are going through. Despite the AIH community being small, there are plenty of patients on social media via the Autoimmune Hepatitis Research Network and the Autoimmune Hepatitis Association. Post a question on there every once in a while. You’ll be surprised by the amount of patients that are willing to help! Plus your AIH friends understand what it’s like to experience stigma with AIH.
Top 10 Patient Issues-
submitted by Craig Lammert, M.D. 12/12/15 I recently finished writing a paper about some of the most challenging treatment situations among patients with AIH. Here's a quick top 10 of important issues that plague a significant portion of AIH patients (many which we discuss on here commonly): 10. All patients with AIH deserve consideration of treatment. 9. Those with mild disease and asymptomatic should be considered for treatment, as with time most will become symptomatic and have progressive liver inflammation and fibrosis. 8. Approximately 15% of AIH patients will require 2nd line medications to control disease (for a number of reasons). 7. There is no established algorithm for the right drug after first line treatment with prednisone +/- Azathioprine. Bottom line, find one that works and the patient will tolerate it. 6. Intolerance to Azathioprine is a sizable issue in up to 10-15%, and many will need to move to another agent because of this issue. 5. Mycophenolate mofetil is likely a good 2nd line agent for those with Azathioprine intolerance because of GI side effects or cytopenias, but not for patients that have poor response to Azathioprine. 4. Budesonide is likely a good alternative for prednisone in treatment regimens, yet is contraindicated in patients with cirrhosis. 3. Caution with use of Mycophenolate mofetil in any patient that could potentially be child bearing age (meaning 2 forms of birth control and random urine pregnancy screens). It is a teratogen in pregnancy. 2. Treatment of AIH through pregnancy with appropriate agents is likely a good idea as up to 1/4 will flare in early and up to 1/2 will flare after delivery. 1. Goal of treatment: normal AST and ALT, normal IgG. Completion of this within 6 months to a year tend to be associated with normalization of inflammation in the liver and possibly fibrosis improvement in about half of patients (still needs more data). |
Holly King offers her insights into having a supportive and open relationship with your medical team.
“I had my labs done, but I haven’t heard anything from you.” As Dr. Lammert’s clinical nurse, this is one of the most common things our patients say to me. Working at Indiana University Health, we have Autoimmune Hepatitis patients who come to us from all over the country for their care. Often, there is additional testing that is needed after their appointment and it is much easier on some patients to have that testing closer to home. We send orders to facilities all over the country for labwork and testing to be done, but unfortunately, the results do not always get to us. This can cause a delay in care, and frustration for patients and their care team. In our practice, patients are a key part of this care team and the more engaged they are in their care, the better we are able to help them achieve overall wellness. One of the key things that I tell patients when I am sending lab orders out is if they have not heard from me within a week of having labs drawn or testing done is that I want them to call and let me know. Often, the reason patients have not received results from our office is because I have not received them from the lab! If there is another reason that there is a delay in results being communicated, I will call patients back and let them know why and when they can expect to hear from us. One of the best things that I see our engaged AIH patients do, is keep their own records of their labs and testing. Bringing the copies of your most recent results to every appointment ensures that if anything has been missed, it is available for your doctor to view right then. Most large health systems (including IU Health) now have secure electronic patient portals that let patients view their results online. Signing up and using this tool empowers patients with easier access to results and the ability to email their physicians and nurses. I love being able to replace playing “phone tag” for several days with an email! Communication between physician, nurse, and patient should be the foundation of your medical care. Some patients feel like they shouldn’t “bother” their doctor’s office with questions about results, but staying proactive is one of the ways that patients can impact their treatment. Yes, doctors and nurses are busy, but patients should always feel like they are a key member of their care team. If you don’t feel that is happening, I encourage you to talk with your team about how to improve your communication. With a lifelong disease like AIH, having an open and supportive relationship with your medical team is one of the keys to good outcomes. 
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Stress and AIH- submitted by Craig Lammert, MD 11/23/2015
Stress and autoimmune hepatitis – What's the link? We have talked on this topic previously here, and even reported results from a 2010 study showing AIH patients were more likely to have a stressful event in their life prior to a relapse episode of disease. A group from Yale provides a possible physiologic mechanism behind this observation, presented at AASLD poster session.
Macrophage migration inhibitory factor (MIF), is a molecule that can help stimulate an overactive immune system. Recently, increased MIF levels have been seen in AIH patients. In the same study, it was observed that another protein, CD74, can bind MIF and decrease its levels (thereby lowering its immunologic stimulus effect).
MIF can be secreted by the neuroendocrine system, and therefore the authors hypothesized that this molecule could be a part of the “stress induced” risk of AIH disease activity. 32 adult AIH patients and 4 with overlap features (PSC and PBC) were queried about recent stress events, had their baseline liver tests completed, and MIF and CD74 levels measured. Those with higher stress levels in the past 1 and 2 years had higher ALT levels. Also, higher MIFs were associated with the higher ALT groups. Finally, the CD74:MIF ratio was higher in patients with better controlled disease. Among the overlap patients, this association was not significant.
The authors feel this supports MIF as a possible physiologic mechanism of stress and AIH disease activity. My opinion, I am unclear of the importance of this, yet it is interesting. The study is small, and stress events have a large subjective component. I think the study is a long way from showing causation but may give us another reason to “stay calm and carry on”.
Stress and autoimmune hepatitis – What's the link? We have talked on this topic previously here, and even reported results from a 2010 study showing AIH patients were more likely to have a stressful event in their life prior to a relapse episode of disease. A group from Yale provides a possible physiologic mechanism behind this observation, presented at AASLD poster session.
Macrophage migration inhibitory factor (MIF), is a molecule that can help stimulate an overactive immune system. Recently, increased MIF levels have been seen in AIH patients. In the same study, it was observed that another protein, CD74, can bind MIF and decrease its levels (thereby lowering its immunologic stimulus effect).
MIF can be secreted by the neuroendocrine system, and therefore the authors hypothesized that this molecule could be a part of the “stress induced” risk of AIH disease activity. 32 adult AIH patients and 4 with overlap features (PSC and PBC) were queried about recent stress events, had their baseline liver tests completed, and MIF and CD74 levels measured. Those with higher stress levels in the past 1 and 2 years had higher ALT levels. Also, higher MIFs were associated with the higher ALT groups. Finally, the CD74:MIF ratio was higher in patients with better controlled disease. Among the overlap patients, this association was not significant.
The authors feel this supports MIF as a possible physiologic mechanism of stress and AIH disease activity. My opinion, I am unclear of the importance of this, yet it is interesting. The study is small, and stress events have a large subjective component. I think the study is a long way from showing causation but may give us another reason to “stay calm and carry on”.
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Research Opportunity
The cause of autoimmune hepatitis (AIH) is poorly understood, however it is believed to be a result of genetics and environmental risk factors. We are interested in studying both components in order to better understand why AIH develops in some people and not in others. Our research group at Indiana University, under the lead of Dr. Craig Lammert, would like to invite you to become a part of the GRACE (Genetic Repository of Autoimmune Liver Disease and Contributing Exposures) Study. Our aim is to collect and examine both genetic material and questionnaire responses from both patients with AIH and healthy people. To be included, you must have been diagnosed with AIH or AIH overlap disease (AIH – primary biliary cirrhosis or primary sclerosing cholangitis), currently at least 18 years of age and live within the United States. If you are interested in finding more information about this study or to enroll, please email or call Joshua Love at josdlove@iu.edu or 317-278-9387. |
Gastrointestinal Side Effects of Azathioprine (AZA, Imuran)
First line treatment, Azathioprine (AZA) (aka Imuran) along with prednisone gives good biochemical (liver tests) response in many patients with autoimmune hepatitis - that is, IF it’s tolerated well. AZA has historically been an issue for some because of intolerance; this includes gastroenterologic side effects (nausea, abdominal discomfort) and cytotoxicities (low white, red, and platelet cell counts) to name a few. Those in this unfortunate group are commonly left to move on to other drug classes as another attempt to control liver inflammation (classes that have historically called nonstandard or 2nd line therapies). This may not be an issue, yet these nonstandard approaches have far less data from scientific studies behind them.
Interestingly, the field of inflammatory bowel disease has also realized the challenges of Imuran to treat inflammation. There have a few studies in this area (Crohn’s and Ulcerative Colitis) that have looked at the tolerability of 6-mercaptopurine (6-MP), a drug that is a step down from AZA. (see the attached figure, 6-MP is formed in the body when AZA is first degraded). In inflammatory bowel disease studies, approximately 50% of patients were able to tolerate 6-MP, even with prior AZA intolerance.
A study just published including both UK and German patients (22 in total AIH patients and 6 AIH-overlap) sought to see if the 6-MP use after stopping AZA because of intolerance (only for symptoms and not cytopenias) in autoimmune hepatitis. Of the 22 AIH patients, approximately ¾ of patients were able to tolerate 6-MP despite previously having side effects from AZA. In total, about 70% of patients on 6-MP in this group were able to achieve complete biochemical response. There were 5 patients that had intolerance to 6-MP, all of them had obvious side effects of treatment within 1 month of treatment start. In terms of the overlap cases, 2 of 6 patients were able to tolerate 6-MP and had good biochemical response.
What does this mean? In my opinion, this is similar to ratios seen in my practice at Indiana. Given the older IBD data, I have always given folks a chance on 6-MP if AZA caused significant symptoms. Many do well. This study supports that patients that have to stop AZA because of severe side effects (mostly gastro) have a good chance of tolerating the 6-MP drug, and won’t have to necessarily go to other medications such as CellCept, Everolimus, Sirolimus, Cyclosporine, etc. I believe this is good, as moving to new medications reveals new compounds that have their own side effect profile and have limited biochemical response data. Furthermore, these drugs can be expensive, and specifically, CellCept, is contraindicated in pregnancy because of its risk of birth defects.
So I must ask, “Have you had a gastrointestinal side effect related to AZA – nausea, vomiting, diarrhea, abdominal pain, etc?” and “did your doctor change you to 6-MP as a follow up medication (outside of prednisone or budesonide)?”. If you weren’t changed to 6-MP, “what medication was used after AZA?”.
First line treatment, Azathioprine (AZA) (aka Imuran) along with prednisone gives good biochemical (liver tests) response in many patients with autoimmune hepatitis - that is, IF it’s tolerated well. AZA has historically been an issue for some because of intolerance; this includes gastroenterologic side effects (nausea, abdominal discomfort) and cytotoxicities (low white, red, and platelet cell counts) to name a few. Those in this unfortunate group are commonly left to move on to other drug classes as another attempt to control liver inflammation (classes that have historically called nonstandard or 2nd line therapies). This may not be an issue, yet these nonstandard approaches have far less data from scientific studies behind them.
Interestingly, the field of inflammatory bowel disease has also realized the challenges of Imuran to treat inflammation. There have a few studies in this area (Crohn’s and Ulcerative Colitis) that have looked at the tolerability of 6-mercaptopurine (6-MP), a drug that is a step down from AZA. (see the attached figure, 6-MP is formed in the body when AZA is first degraded). In inflammatory bowel disease studies, approximately 50% of patients were able to tolerate 6-MP, even with prior AZA intolerance.
A study just published including both UK and German patients (22 in total AIH patients and 6 AIH-overlap) sought to see if the 6-MP use after stopping AZA because of intolerance (only for symptoms and not cytopenias) in autoimmune hepatitis. Of the 22 AIH patients, approximately ¾ of patients were able to tolerate 6-MP despite previously having side effects from AZA. In total, about 70% of patients on 6-MP in this group were able to achieve complete biochemical response. There were 5 patients that had intolerance to 6-MP, all of them had obvious side effects of treatment within 1 month of treatment start. In terms of the overlap cases, 2 of 6 patients were able to tolerate 6-MP and had good biochemical response.
What does this mean? In my opinion, this is similar to ratios seen in my practice at Indiana. Given the older IBD data, I have always given folks a chance on 6-MP if AZA caused significant symptoms. Many do well. This study supports that patients that have to stop AZA because of severe side effects (mostly gastro) have a good chance of tolerating the 6-MP drug, and won’t have to necessarily go to other medications such as CellCept, Everolimus, Sirolimus, Cyclosporine, etc. I believe this is good, as moving to new medications reveals new compounds that have their own side effect profile and have limited biochemical response data. Furthermore, these drugs can be expensive, and specifically, CellCept, is contraindicated in pregnancy because of its risk of birth defects.
So I must ask, “Have you had a gastrointestinal side effect related to AZA – nausea, vomiting, diarrhea, abdominal pain, etc?” and “did your doctor change you to 6-MP as a follow up medication (outside of prednisone or budesonide)?”. If you weren’t changed to 6-MP, “what medication was used after AZA?”.
Sleep Disturbance and Fatigue in AIH
The Autoimmune Hepatitis Research Network presented results at the AIH Monothematic Conference from a study that many of you were involved in. Please see the attached poster. Essentially, we have found that fatigue is prevalent in AIH and does not seem to be associated with advanced fibrosis. Furthermore, we see a number of measures of sleep abnormal in AIH patients. Interestingly, the duration of sleep is the same as compared to healthy controls. Screening for sleep disturbance in AIH is important, as well as looking for secondary causes of sleep disorders that can be treated otherwise to impact overall quality of life. Unfortunately, there is much more to this story and it deserves continued investigation.
The Autoimmune Hepatitis Research Network presented results at the AIH Monothematic Conference from a study that many of you were involved in. Please see the attached poster. Essentially, we have found that fatigue is prevalent in AIH and does not seem to be associated with advanced fibrosis. Furthermore, we see a number of measures of sleep abnormal in AIH patients. Interestingly, the duration of sleep is the same as compared to healthy controls. Screening for sleep disturbance in AIH is important, as well as looking for secondary causes of sleep disorders that can be treated otherwise to impact overall quality of life. Unfortunately, there is much more to this story and it deserves continued investigation.
Notes from the EASL AIH Monothematic Conference (and International AIH Group meeting)
Craig Lammert, MD
Recently, the European Association for the Study of Liver published renewed guidelines for AIH, and offers the most up to date instructions to physicians managing this complex disease. You can find the guidelines here: http://www.easl.eu/medias/cpg/2015-09/CPG_AIH_final.pdf
This 34 page document (over 300 references) condenses much of what is known about the disease from clinical/pharmacologic studies and offers insight into approaches to disease management (even among some AIH subgroups). Overall, the goal is to improve care provided to AIH patients across the board. Thus, it remains key that patients and physicians alike are up to date on disease paradigms. However, as the authors to this work would also state, given the rarity of this disease (as well as limited data in a number of areas), guidelines can be developed around expert consensus. In the scope of “medical evidence” this is lower on the scale than compare to the best randomized controlled trial. I would say that all readers of the document should keep the level of evidence in mind when digesting the material, but this may be the best we have for now.
It is hoped that, if you do take a minute to scan this work, you will come across some redundant information you may have picked up from our group discussions. However, we can also use this document to stimulate discussion as well (if there is any foreign material to you).
Craig Lammert, MD
Recently, the European Association for the Study of Liver published renewed guidelines for AIH, and offers the most up to date instructions to physicians managing this complex disease. You can find the guidelines here: http://www.easl.eu/medias/cpg/2015-09/CPG_AIH_final.pdf
This 34 page document (over 300 references) condenses much of what is known about the disease from clinical/pharmacologic studies and offers insight into approaches to disease management (even among some AIH subgroups). Overall, the goal is to improve care provided to AIH patients across the board. Thus, it remains key that patients and physicians alike are up to date on disease paradigms. However, as the authors to this work would also state, given the rarity of this disease (as well as limited data in a number of areas), guidelines can be developed around expert consensus. In the scope of “medical evidence” this is lower on the scale than compare to the best randomized controlled trial. I would say that all readers of the document should keep the level of evidence in mind when digesting the material, but this may be the best we have for now.
It is hoped that, if you do take a minute to scan this work, you will come across some redundant information you may have picked up from our group discussions. However, we can also use this document to stimulate discussion as well (if there is any foreign material to you).
Your Microbiome and Your Liver
Craig Lammert, MD
Similar to the internet and social media, words such as “microbiome” and “leaky gut” are “trending” in scientific thought about liver disease. There has been an explosion of research in the microbiome (the wide variety of billions of bacteria currently living in your intestines right now), and a large percentage has focused on the liver. The liver has 2 blood supplies, yet ¾ of it comes from the portal vein. The portal vein is the major conduit from which all the blood from the intestines drains. This helps to highlight a liver role as a “filter”, as blood is “cleaned” before it goes anywhere else in the body. However, not only nutrients from our diet or drugs we take for conditions go to the liver via this route for processing. It also includes molecules, mediators, and parts of bacteria from the intestine.
It has been proposed that bacterial substances coming to the liver via the portal vein can impact the “natural” state of the liver and activate a number of immune mechanisms that may be involved in initiating disease there. One way that bacteria are thought to get into this blood system from the intestine is by moving between cells that line the GI track (leaky gut).
To date, there has only been data supporting a role for gut microorganisms in AIH in an animal model of the disease (ConA model). There is now new published data in humans with AIH that sought to understand the bacteria’s role in this disease from a Chinese research group.
The study included 24 patients with AIH and 8 healthy volunteers. The investigators sought to understand how the bacteria populations and “gut leakiness” were different between the 2 groups.
What they found:
1. The cellular machinery that helps to ensure integrity and “tightness” of the gut was impaired in AIH patients. Also the amount of key protein from comparative samples was reduced in the AIH patients. . (MORE leaky)
2. Bacterial DNA assessment showed that there was a statistically significant decrease in a few species of bacteria in AIH versus controls: AKA Bacterial dysbiosis. These species were bifidobacertium and lactobacillus.
Words of caution and on interpretation of this data. This is a small study, it helps to support a hypothesis at best. Examination of these 2 findings need to be replicated on a large scale. Also, finding of associations, does not mean causality. This may be only one of a hundred different pieces that goes into the AIH equation. The next question that most will think of is: “do I need to be taking probiotics to help protect against dysbiosis?” My answer would be “no” as it is too early to know of any evidence-based impact on this disease. However, that being said, could this be a strategy for treatment in the future if this data is supported and pathways are eventually worked out: “Maybe”.
Craig Lammert, MD
Similar to the internet and social media, words such as “microbiome” and “leaky gut” are “trending” in scientific thought about liver disease. There has been an explosion of research in the microbiome (the wide variety of billions of bacteria currently living in your intestines right now), and a large percentage has focused on the liver. The liver has 2 blood supplies, yet ¾ of it comes from the portal vein. The portal vein is the major conduit from which all the blood from the intestines drains. This helps to highlight a liver role as a “filter”, as blood is “cleaned” before it goes anywhere else in the body. However, not only nutrients from our diet or drugs we take for conditions go to the liver via this route for processing. It also includes molecules, mediators, and parts of bacteria from the intestine.
It has been proposed that bacterial substances coming to the liver via the portal vein can impact the “natural” state of the liver and activate a number of immune mechanisms that may be involved in initiating disease there. One way that bacteria are thought to get into this blood system from the intestine is by moving between cells that line the GI track (leaky gut).
To date, there has only been data supporting a role for gut microorganisms in AIH in an animal model of the disease (ConA model). There is now new published data in humans with AIH that sought to understand the bacteria’s role in this disease from a Chinese research group.
The study included 24 patients with AIH and 8 healthy volunteers. The investigators sought to understand how the bacteria populations and “gut leakiness” were different between the 2 groups.
What they found:
1. The cellular machinery that helps to ensure integrity and “tightness” of the gut was impaired in AIH patients. Also the amount of key protein from comparative samples was reduced in the AIH patients. . (MORE leaky)
2. Bacterial DNA assessment showed that there was a statistically significant decrease in a few species of bacteria in AIH versus controls: AKA Bacterial dysbiosis. These species were bifidobacertium and lactobacillus.
Words of caution and on interpretation of this data. This is a small study, it helps to support a hypothesis at best. Examination of these 2 findings need to be replicated on a large scale. Also, finding of associations, does not mean causality. This may be only one of a hundred different pieces that goes into the AIH equation. The next question that most will think of is: “do I need to be taking probiotics to help protect against dysbiosis?” My answer would be “no” as it is too early to know of any evidence-based impact on this disease. However, that being said, could this be a strategy for treatment in the future if this data is supported and pathways are eventually worked out: “Maybe”.
