to the liver meeting 2020 and the Hepatology Associates SIG program. Interdisciplinary approach to managing metabolic syndrome in NAFLD NASH patients. The first half of this comprehensive program will focus on the diagnosis and management of NAFLD NASH patients and review the new therapeutic options approved and in clinical trials for the treatment of NASH. The second half will focus on metabolic syndrome, including approaches to assess cardiovascular risk treatment guidelines for hypertension and hyperlipidemia and a primer for type two diabetes management. Before we get started, I just wanna remind you about the format of the session. This program includes four pre-recorded presentations. During the presentation, attendees and speakers will be able to engage with one another utilizing the chat feature. Please place any questions you have for the speakers in the chat feature. This slide summarizes the four talks within the program. We will begin with Anthony Durencius speaking on the diagnostics for NAFLD and NASH followed by new therapeutics for NASH by Jane Jung. Then April Morris will assess cardiovascular risks and treatment guidelines for hypertension and hyperlipidemia. And we will conclude with Don Percy and Catherine Evans-Kreider on the identification and initial treatment of type two diabetes in NAFLD and NASH. Although the meeting looks different this year, we hope you enjoy this informative session. Thank you. Hello, and welcome to the Hepatology Associates SIG Programming. I'm gonna start off this topic with a presentation on the diagnostics of NAFLD and NASH. A little bit about myself. My name is Anthony Durencius. I'm a physician assistant at the Texas Liver Institute in San Antonio, former awardee of the 2018 NPPA Clinical Hepatology Fellowship. Here are my disclosures. The objectives for today's presentation are listed below. We're gonna define NAFLD. We're gonna be able to understand the difference between NAFL and AFL and NASH. Number two, identify non-invasive tools tests that can aid in the diagnosis of NAFLD. And lastly, recognize the role of liver biopsy and how to interpret results. We'll begin by talking about the spectrum of non-alcoholic fatty liver disease. So NAFLD, kind of the definition, this is a spectrum of liver disease characterized or defined by hepatic steatosis in those that do not consume heavy quantities of alcohol. We will define that here shortly. NAFLD as a spectrum, as I mentioned, kind of has different ways that we can describe it. So going from left to right, hepatic steatosis, most benign and first kind of step. This is gonna be defined by a greater than 5% steatosis without evidence of any cellular injury, inflammation, or fibrosis. This is also known as simple steatosis, non-NASH fatty liver, or simply non-alcoholic fatty liver. This is different from NASH, non-alcoholic steatohepatitis. This is more than 5%, more than or equal to 5% with the presence of cellular injury inflammation on pathology or liver biopsy. This could be with or without fibrosis. And lastly, we have NASH cirrhosis. So this is now progression of steatosis to end-stage disease with or without portal hypertension. However, on pathology, we may not see any more steatosis, maybe what we call burned out. This slide talks about different causes of fatty liver. Specifically with NAFLD, we're gonna be talking about this first period or first area of emphasis. So this is our metabolic factors that lead to NAFLD. So things we know, metabolic syndrome, diabetes, hyperlipidemia, obesity. This is what I'm gonna call true NAFLD. New terminology, they're kind of going towards more MAFLD or metabolic-associated fatty liver disease. But other metabolic factors like PCOS, we have genetic factors, Wilson disease, mitochondrial diseases. There are known medications and toxins that can lead to fatty liver. This would not be true at NAFLD, however. And lastly, we know there's other liver disease, other liver conditions, such as alcohol, such as hepatitis C. We think with hepatitis B and even PBC with the dysfunction of lipids, this can also present with steatosis. You can have a combination. You can have both hepatitis and NAFLD, for example. So for this presentation, mostly we're gonna talk about just true NAFLD. I wanna talk about some non-invasive diagnostic tools now. So starting off, diagnosis of NAFLD and simple steatosis, we need to have a clinical suspicion, some risk factors. So going back a moment ago, talking about metabolic syndrome risks, we need to rule out significant alcohol. So as I mentioned earlier, kind of the guidance and recommendation or cutoff for a significant alcohol is anything more than 14 to 21 standard drinks per week in males, anything more than seven to 14 standard drinks in females. We think maybe even less than this could be pathologic for fatty liver, necessarily NAFLD or alcoholic related. And then lastly, we need some sort of imaging, simple imaging that can show a hepatic steatosis. In clinical practice, which I see day to day, we'll see a simple ultrasound showing signs of steatosis. Up to 30% of steatosis or more can be seen on a simple ultrasound. Less than that, it may not be caught. On the ultrasound itself, you'll see a brighter liver. You'll see echo texture that's greater than the kidney if we're comparing them. And then talking about the vascular blurring, when we look at the liver itself, we won't see quite as well the vasculature vessels. Both CAT scan MRI can also pick it up. CAT scan also 30% or more can very easily see fatty liver. The pros to a CAT scan over an ultrasound, for example, it will be in the obese population. Drawbacks, however, this is cross-sectional, more costly imaging. There is radiation involved. Typically it's with or without contrast. MRI scan, even more accurate, as low as 5% of steatosis. So that cutoff for truly making diagnosis of NAFLD, like I said, 5% or more. We can get down that low with an MRI scan. It's also been shown and we use it in a lot of clinical trials. It's well-validated. Downside, however, is it's very costly. It may not be fully accessible wherever you're at. And tolerability to patients may not be the best either, you know, holding breath or just, you know, remaining still for maybe a more lengthy time during an MRI scan. We know routine imaging alone, so just simple ultrasound, CT scan, MRI alone, cannot be used to determine or diagnose NASH, however, and definitely cannot determine whether there's the presence of fibrosis. So going into other options or other tests and tools, like as mentioned, there are plenty of biomarkers or lab-based tests that can help us out here, starting off with the ALT. I mean, this is immunotransferase that we see can be elevated in any chronic liver disease or something causing inflammation. But in patients with NAFLD, especially on the lower end of the spectrum, may have a normal ALT. We can see up to 60, 70% of patients with a normal ALT. Some other ones used more so in research, not necessarily clinical practice, although they do, we use them in combination with things like CK18. This is a marker of apoptosis. We have cetokines, edepokines. These can be seen in pathogenesis of NAFLD. There are a lot of inflammatory markers, alpha-2 macroglobulin, for example. We can see elevation of CRP. And measuring markers of insulin resistance, home IR, for example, you know, this is independently linked to fatty liver as well. But not one biomarker, as I mentioned, is used alone to differentiate simple steatosis or non-alcoholic fatty liver versus NASH. There are many predictive models, complex diagnostic combo panels that we see and we use and are available in clinical practice, things like the NASH test or using a NASH CRN model. A lot of these have not only lab, but also demographic and information about the patient. At this time, we don't really have recommendations for one or the other. It can help us, you know, put someone in a period of thought, but it's not necessarily diagnostic alone. This differs slightly from our NASH, NASH from fibrosis biomarkers. So there are a lot of biomarkers we look at for fibrosis. We know that, you know, the more fibrosis we see with fatty liver, the different prognosis, just kind of the change in concern with clinical course and natural course of the disease. So there are markers of fibrogenesis, as mentioned on this top bullet. We know, and maybe more up and coming, much to learn on different micro RNAs. Presence of certain RNAs show the evidence of regulation of lipid metabolism, oxidative stress, inflammation. These can show both pictures and evidence in NASH and or fibrosis. And indirect markers, more alteration of hepatic function, how much damage, inflammation. You know, these are simple things you'll see on a metabolic panel. Aminotransferases, ALKFOS, GGT, albumin, bilirubin, et cetera. There are better validated predictive models for fibrosis. There's all kinds of lab-based biomarkers. ASLD does support using these to help guide clinical decision-making or help determine if, you know, treatment is warranted or further diagnostic studies are needed. They're overall better to rule out disease. So for example, NAFL fibrosis score, FIB4, a low value being, you know, less than negative 1.455 on the NFS, negative 1.3 on the FIB4, kind of helps us exclude the presence of NASH fibrosis and help us, you know, maybe not be as concerned to help treat the patient a little bit differently. We have plenty of, you know, technologically and what I call special liver imaging tests or studies. These are things like transient elastography, better known as FibroScan. This is a mechanical vibration controlled test or tool, readily available, commonly available. We have one in our practice. Both the transient elastography itself can measure steatosis with what we call the controlled attenuation parameter or CAP. It also obviously can measure fibrosis scoring. We have a tool, shear wave acoustic elastography, better known as ARFI. And this is an ultrasound-based test. It can help give us both a picture. So we got some imaging and fibrosis scoring on this. And then the best is actually continuous elastography, so things like MRI scan. It's the most accurate. We know that little changes in the MRI markers of steatosis fibrosis can correlate very well with a change in the amount of fat and the amount of steatosis and damage. Again, this is just a matter of, you know, accessibility and do you have it near you. Overall, it's kind of an interpretation of the common special liver imaging and the ones I just mentioned. So in orange here, we'll see CAP, we'll see MR, PDFF, spectroscopy. These are all measures of steatosis. I have a normal cutoff, so anything less than that generally will be ruling out any significant steatosis or in the green, the fibrosis. The color-coded numbers here, so in orange S3, if it's 302 or higher for fibroscan CAP, this may predict more severe steatosis. Going down to ARFI, fibroscan, the liver stiffness measurement, MRE measured in kilopascals, you can see kind of similar numbers. This has been well studied. There are numerous studies on this, measuring in different patient populations, looking at specifically in NAFLD patients. So this is ever, not necessarily ever changing, but definitely you'll see different numbers on different things. So it's a wide range, but this is a pretty good summary, if you ask me. I want to go down to more invasive tools. Specifically, I want to talk about liver biopsy. So liver biopsy is still the gold standard for characterizing and determining histology in fatty liver. Textbook answer is to really make the diagnosis of NASH, we should have histology to guide us, so biopsy would be warranted. It should also be considered in patients at increased risk. So those that, you know, with those high risk factors and potentially these non-invasive markers, whether biomarkers, labs, and or special imaging kind of predicts maybe a higher thing to confirm and also to help benefit diagnostically, prognostically help guide treatment. I can also rule in and rule out other competing etiologies if you think there could be more than one thing going on. The methods of doing a biopsy, I mean, the core sample is much more favorable and a better sample than a wedge. You can do it percutaneously, it can be done laparoscopically during a open procedure or a laparoscopic procedure. It can be done endoscopically, so this is usually endoscopic ultrasound guided. And we can also do transvenous, so we can do it transjugularly, transformorally. Benefit of doing a transjugular release, you can also measure potentially hepatic venous pressure gradients. The cons or the downsides with a liver biopsy, it is invasive, there's some costs to it as well that we may overlook. Definitely symptoms afterwards, so pain, irritation, there's risk of bleeding with this procedure. You can have also sampling errors, so this is something that, although it's the gold standard, you may not get a good sample. Typically you want at least a good 10 portal track sample, core again over wedge, and be able to kind of fully look at these hepatic globules on the biopsy itself. On the biopsy for fatty liver, we're gonna see steatosis by definition or by view, it'll show up as droplets of extra fat in the liver. Typically with non-alcoholic fatty liver disease, it is gonna be large or macrovesicular droplets. It will not be as small as maybe with other etiologies. You can have a mixed pattern as well. It may not just be the large macrovesicular. With NASH, there definitely will be inflammation by definition. It'll start more lobular, and then it can also be seen in the portal aspect of it. It can be mixed, so different inflammatory cells and markers you'll see on the sample. There could be some mononuclear cells as well. And then kind of pathognomonic, we call this ballooning of the hepatocytes. There it gets swollen, not as much cytoplasm in them. And then also there may be these findings called malarie-dunk bodies. These are kind of aggregates of eosinophilic material that will be seen in the ballooned hepatocytes as well. With liver biopsy, just like we mentioned with the special liver imaging studies, we have different scoring systems and scoring markers. We have different ones. So some well-known ones would be the Brunn classification, going through steatosis, inflammation, ballooning, what class for each column or each finding on the biopsy sample itself. So mild is typically, as you'll see throughout this thing, less than 33%, moderate being 33 to 66%, more than 66% is considered severe steatosis. When we mentioned S1, S2, S3, on comparison with those special imaging studies, that's kind of what we're comparing it to. It's this marker of steatosis, whether it's Brunn class or going down further to this NAFLD activity score. How much inflammation? NPF is for medium power field. So how many foci of inflammation? And then ballooning, is it present? Is it marked? Typically zone three. With the NAFLD activity score, slightly different. Normal is less than five versus none. We have an interpretation part here as well. So you have a little bit of steatosis, a little bit of inflammation. You typically need that ballooning. It's kind of a prerequirement. And NAFLD activity score should be over five to truly say that this is NASH. Score is three to four. It can be kind of borderline. It can be mild NASH. A lot of time it's open to interpretation by the pathologist, but you have someone with borderline NASH, but all the risk factors, I would call it NASH, can always have the slide over it and determine if this fits that over five or more NAFLD activity score measurement. In terms of the fibrosis, so that was all more of the NASH components. So for fibrosis, the NASH Clinical Research Network, CRN, breaks it into this F0 to F4 categorization. We know F0 to F4 is kind of that metavere scoring. With F1, we talk about, it can be perisinusoidal or periportal fibrosis, mild-moderate, and then when it gets to that portal-periportal aspect at 1c. Bridging fibrosis is classically stage 3, F3. And then F4, final stage, will be cirrhosis. Here are some pictures to kind of show you along with it. An alternative scoring system is what we call the SAF score, SAF classification, steatosis activity fibrosis score. Activity is kind of a combination of the inflammation and the ballooning scene, but very similar in nature with the NAFLD activity score, as you saw in the slide prior to this. Using this steatosis activity fibrosis score, however, you need ballooning as well to call this NASH. So, a minimum steatosis score 1, 2, 3, as I follow the arrows along. With at least one ballooning, I would need at least one inflammation, and then that can call this NASH. Anything without ballooning and with minimal inflammation could be just simply NAFLD and something else ongoing. So, to kind of summarize and give you some key takeaways from this presentation, you know, NAFLD, by definition, encompasses a spectrum of fatty liver disease, going from steatosis to NASH to NASH cirrhosis. Appropriate diagnosis can help prognosticate and predict the course. Obviously, NASH and or fibrosis are patients that we want to identify. There are numerous noninvasive modalities to aid in prediction of where someone will fall on the spectrum. It starts off with simple routine imaging, clinical suspicion. We have biomarkers available, and then we have these special imaging tests, as I mentioned earlier. Lastly, liver biopsy, though, still plays a big role in diagnosing not only NASH, but confirming specific fibrosis, helps guide us in therapeutics. And really, when we talk about upcoming treatments, which will be a presentation after mine, you know, it'll help guide us in treatment, you know, response and treatment goals, etc. Thank you guys for paying attention. Enjoy the rest of the liver meeting, and I appreciate it. Thank you. My name is Jane Jiang, and I'm a clinical pharmacist practitioner at UNC Health. I want to thank the AASLD Associates SIG for inviting me to speak today on the topic of new therapeutics for non-alcoholic steatohepatitis. I do not have any financial disclosures, but I will be talking about non-FDA-approved indications, as well as medications in clinical trials. The objectives of this talk is to briefly summarize the current treatment options for NASH and to review new therapeutic options currently in clinical trials. NASH is a complex disease involving many pathways affecting lipid metabolism, inflammation, and fibrosis, among others. In addition to fat accumulation in liver due to impaired lipid metabolism, underlying metabolic syndromes such as obesity and insulin resistance can create metabolic stress and lead to lipotoxicity, which in turn can generate inflammation. Inflammation is necessary to repair liver injury, but it can lead to fibrosis and put patients at risk of developing cirrhosis and liver-related complications. So what can we offer our patients? For many years, lifestyle modifications consisting of diet and exercise have been the cornerstone of treatment, but the key to improvement in NASH is overall weight loss. Studies have shown that weight loss of even 3-5% had improvements in steatosis. However, a greater weight loss of 7-10% is needed to improve the majority of the histopathological features of NASH, including fibrosis. Even though weight loss can be effective, it is often difficult to achieve and sustain. So to date, there are no FDA-approved pharmacological agents for treatment of NASH. However, there are several that have been evaluated and mentioned in the AASLD practice guideline that I wanted to briefly review. First is metformin. Although several studies have shown an improvement in liver enzymes, meta-analysis concluded that metformin did not improve liver histology in NASH patients. Therefore, currently, metformin is not recommended for treating NASH in adult patients. Thiazolidinediones, such as pyoglitazone, is thought to increase uptake of fatty acids by adipocytes rather than uptake by organs such as liver. It has shown to improve liver histology in patients with and without type 2 diabetes. However, there are side effects associated with pyoglitazone, such as weight gain, fluid retention, and bone loss in women. Until further data supports the safety and efficacy guidelines state, it may be used to treat only in biopsy-proven NASH. GLP-1 analogs, such as laryngotide, has shown improvements in weight, glucose level, and HDLs with minimal adverse effects in patients with biopsy-proven NASH. However, the guidelines state it is premature to consider GLP-1 agonists to treat NASH. Vitamin E at daily doses of 800 IU per day has shown to improve liver histology in non-diabetic patients with biopsy-proven NASH and can be considered for treatment. However, there's been some concerns regarding long-term safety of vitamin E. Therefore, risks and benefits should be discussed, and guidelines specifically recommend not to treat in diabetic patients or in NASH cirrhosis. Several proof-of-concept studies have also looked at ursodeoxycholic acid in patients with NASH, but a large multi-center randomized control study did not find any histological benefit over placebo. Therefore, a guideline does not recommend using this for treatment of NASH. Omega-3 fatty acid, which is currently FDA-approved to treat hypertriglyceridemia, have been also studied in NASH, but studies failed to show benefits. Again, the guidelines state that the omega-3 fatty acids should not be used for NASH, but may be considered to treat hypertriglyceridemia in patients with NAFLD. Given the strong association between NAFLD and increased risk of CVD events, statins have also been looked at. Clinical trials of statins for treatment of NASH are limited with inconsistent results, but several studies showed safety of statins in patients with liver disease, regardless of baseline elevations in liver enzymes, and that patients with NASH are not at higher risk for serious liver injury from statins. Therefore, statins can be used to treat dyslipidemia in patients with NASH. So what can we look forward to? The good news is that there's been many advances in the past few years in discovery of novel agents that address these key targets of lipid metabolism, inflammation, and fibrosis. Today, I'm hoping to give you an update on some of these agents. Ovated colic acid, or OCA, may be one of the agents that you may have been hearing about in the pipeline. This is a farnesoid X receptor, or FXR agonist, which plays a role in bile acid and metabolism, leading to decreasing hepatic steatosis and also thought to reduce fibrosis and inflammation. You may have been familiar with its current FDA indication for primary biliary cholangitis. OCA's phase two trial, the Flint study, met its primary endpoint of improving improvement in NAFLD activity score, or NASH, by greater than or equal to two points without worsening of fibrosis and also showed fibrosis improvement. That has led to phase three trial, the REGENERATE study. The REGENERATE study included patients with NASH of at least four and fibrosis stage F2 or F3, or F1 with at least one comorbidity, such as obesity, type 2 diabetes, or ALT greater than 1.5 times upper limit of normal. The exclusion criteria consisted of patients with cirrhosis, any other causes of chronic liver disease, and those who had elevated alcohol consumptions. The study randomized one-to-one-to-one ratio into placebo, OCA 10 milligram and OCA 25 milligram with the liver biopsy evaluation occurring at screening, month 18, for the interim analysis, month 48, and end of study. The primary endpoint of the study are improvement in fibrosis with no worsening of NASH or NASH resolution with no worsening of fibrosis. The interim 18 months result showed that improvement in fibrosis endpoint was achieved by 12% of placebo, 18% in OCA 10 milligram group, and 23% in OCA 25 milligram group for the intent to treat population. Proprotocol population had slightly higher improvement noted with 28% in OCA 25 milligram group compared to 13% in placebo. However, the NASH resolution with no worsening fibrosis endpoint was not met in both intent to treat and proprotocol population. Notable secondary endpoints achieved by the OCA 25 milligram treatment group include improvement of fibrosis by greater than one stage or resolution of NASH without worsening of either, no worsening of fibrosis and no worsening of NASH, improvement of NASH by greater than or equal to two with no worsening fibrosis, improvement of fibrosis and resolution of NASH as composite endpoint. As for the safety population, the most common adverse event was pruritus, and they were generally mild to moderate in severity. Although increase in LDL cholesterol was noted in OCA treatment groups, incidence of cardiovascular adverse events and serious adverse events were similar across the groups. With the positive interim analysis results, Intercept had submitted the new drug application to FDA back in September of 2019. However, in June this year, the FDA has determined that the predicted benefit of OCA based on these endpoints remained uncertain and does not outweigh the potential benefit for accelerated approval. Instead, the FDA recommended that Intercept submit additional post-interim efficacy and safety data from the Regeneron study. The most recent MON24 interim analysis data were released, and these datas include changes from baseline to MON24 in ALT, AST, GGT, FIF4, APRI, and the liver stiffness as measured by FibroScan vibration-controlled transient elastography. These data show us that the mean values of these transaminases improved, and these improvements were sustained after 24 months of therapy in OCA 25 mg group compared with placebo. Liver stiffness after 24 months of therapy also showed a mean difference of 2.7 kilopascals between OCA 25 mg and the placebo. The adverse event profile with MON24 data remained consistent with what was previously reported, and no new safety signal appeared. The Regeneron study remains ongoing at this time. Next, we'll review elefibonor. Elefibonor is a dual peroxisome proliferator activator receptor, or PPAR, alpha delta agonist. You may have heard of the phase 2 GOLDEN study, which did not meet its primary endpoint in intent-to-treat population. However, the post-hoc analysis had shown that NASH resolution without fibrosis worsening in elefibonor 125 mg versus placebo in modified definition. This has led to the phase 3 trial, RESOLVIT. This study evaluated the effect of elefibonor compared to placebo in 1,070 patients with biopsy-proven NASH. These patients had NASH greater than or equal to 4, fibrosis stage F2 or F3. Patients were randomized 2 to 1 to receive elefibonor 120 mg or placebo once daily. The primary endpoint was to evaluate the resolution of NASH without worsening of fibrosis with a follow-up liver biopsy at week 72. In May of this year, results from the interim analysis were released, which showed that the RESOLVIT study did not meet the primary endpoint of NASH resolution without worsening of fibrosis. In addition, on one of the key secondary endpoint of fibrosis improvement of at least one stage, it also did not show any significant differences compared to placebo. In July, GenFit announced that they will be terminating the RESOLVIT trial. Let's review another agent in phase 3 trial. Senequivirac is a dual antagonist of chemokine receptor type 2 and 5. Senequivirac is thought to have both anti-inflammatory and anti-fibrotic activities. It was evaluated in SENTOR phase 2 study, which also did not meet its primary endpoint of greater than or equal to 2 point improvement in NASH for intent to treat population. However, it did show significant improvement in fibrosis without worsening NASH compared to placebo. Aurora is the phase 3 trial for Senequivirac, which will include biopsy-proven NASH patients with F2 or F3 fibrosis between the ages of 18 to 75 years old. In this study, patients will be randomized 2 to 1 to Senequivirac 150 milligrams or placebo once daily. This study will have two parts. Part 1's primary endpoint will be to evaluate the improvement in fibrosis by at least one stage and no worsening of steatohepatitis at month 12, which is expected to complete around October of 2021. And part 2 will evaluate the composite endpoint of histopathologic progression to cirrhosis, liver-related clinical outcomes, and all-cause mortality. Resmideram is a thyroid hormone receptor or THR beta agonist. THR beta is highly expressed in hepatocytes and has shown to play an important role in reducing cholesterol and triglycerides. Because of its selectivity for THR beta, we would not see systemic effects of thyroid hormone in hearts and bones that are largely mediated by THR alpha. Phase 2 clinical trial data were published in Lancet last year. What's different about this study from others is that in addition to screening biopsy, patients were also required to have at least 10% hepatic fat at baseline assessed by MRI proton density fat fraction or MRI-PDFF to be eligible. The primary endpoint was change in hepatic fat compared with placebo at weeks 12 and 36 assessed by MRI-PDFF. The resmideram arm did show relative reduction of hepatic fat compared to placebo at both week 12 and 36. This has led to the Maestro-NASH phase 3 trial, which is expected to enroll 900 patients with biopsy-proven NASH with fibrosis stage F2 or F3. Patients will be randomized 1-1-1 to receive resmideram 80mg or 100mg or placebo once daily. Primary endpoints are also two parts here. Part 1 is NASH resolution with at least 2 point reduction in NAS and with no worsening of fibrosis which will be measured by biopsy at week 52 and expected to complete around June 2021. Part 2 will be looking at composite long-term outcome events including all-cause mortality, cirrhosis, and other significant liver related events. Key secondary endpoints also being studied include liver fibrosis improvement of at least one stage with no worsening NASH as well as lowering of LDL cholesterol. Maestro-NAFLD 1 is another 52-week phase 3 trial of resmideram. Unlike the Maestro-NASH, Maestro-NAFLD 1 is a non-biopsy study and is to represent a more real-life NASH population. Presumed NASH is documented using historical liver biopsy or non-invasive techniques including FibroScan and MRI-PDFF, and patients will be randomized one-to-one-to-one to receive res mid around 80 milligrams, 100 milligrams, or placebo. Primary endpoint will be to evaluate the safety information to support the NASH indication, as well as to provide additional data clinically relevant, such as LDL cholesterol, acryl lipoprotein B, and triglyceride lowering and reduction of liver fat as determined by MRI-PDFF. Dapagliflozin is a sodium glucose co-transporter 2, or SGLT2 inhibitor, which is an FDA-approved treatment regimen for type 2 diabetes. Dapagliflozin reduces reabsorption of glucose from the proximal renal tubules, resulting in increased urinary excretion of glucose and reducing the plasma glucose concentrations. Studies have also shown that dapagliflozin can decrease body weight, total body and visceral fat mass, and reduce serum ASD and ALT level. Dapagliflozin efficacy and action in NASH, or DEAN, is the phase 3 trial that will enroll 100 patients with type 2 diabetes with hemoglobin A1c less than 9.5%, who has biopsy-proven NASH. Arumcol is a steroid co-A desaturase inhibitor, which is thought to down regulate steatosis and fibrosis. Its phase 2 study, the AREST study, looked at percent change in liver fat by MR spectroscopy and found that Arumcol's 600 milligram arm had significant reduction. ARMR, the phase 3 trial, will be recruiting 2,000 patients and randomized to 2 to 1 ratio of Arumcol 300 milligrams twice a day versus placebo. This study will include F2 or F3 NASH patients who are overweight or obese and have prediabetes or type 2 diabetes. This study is also two-part designed with the first part evaluating the resolution of NASH with no worsening fibrosis or improvement in fibrosis with no worsening of NASH after 52 weeks. The second part will continue up to 5 years to measure the composite long-term outcomes. We have gone over our current treatment options for NASH and also several pharmacological agents targeting different mechanisms currently in phase 3 clinical trials. The key takeaways from this talk are despite several potential treatment options, there is still no FDA approved treatments for NASH. Even though there are several phase 3 trials in progress, it still will be a while before any FDA approved agents become available. Lastly, many clinical trials are being conducted with single agent therapy, but based on complex pathophysiology of NASH, combination therapy may be warranted. And I thank you for your attention. Hi, I'd like to thank the organizers for giving me the opportunity to speak today. My topic is assessing cardiovascular risk in NAFLD NASH patients and treatment guidelines for hypertension and hyperlipidemia. My name is April Morris. I'm a nurse practitioner and I currently work at Hunter Holmes McGuire VA in Richmond, Virginia. These are my financial disclosures and these are my objectives that we'll go over in detail today. The first objective, cardiovascular risk associated with NAFLD. Now we're very familiar with the risk factors associated with NAFLD. If you look to the far left, the most common and well established conditions that are associated with NAFLD, things like obesity, type 2 diabetes, dyslipidemia, metabolic syndrome, and polycystic ovarian syndrome. These risk factors are also strongly associated with cardiovascular disease. NAFLD leads to an increased risk of morbidity and mortality from cardiovascular disease. CVD is the leading cause of death in NAFLD patients independent of other metabolic comorbidities. Data show that NASH with fibrosis is associated with the highest risk of cardiovascular disease. Now patients with NAFLD have a pro-atherogenic lipid profile and this is characterized by high triglycerides, high LDL, especially a higher concentration of LDL, small LDL particles, increased APOB, and low HDL. Non-alcoholic fatty liver disease has multiple independent cardiovascular associations which are listed here. For example, young patients with NAFLD have also been seen to have early left ventricular dysfunction, an impaired LV energy metabolism, coronary artery, carotid artery, and peripheral vascular disease in patients with types 1 and 2 diabetes, reduced myocardial perfusion in patients with type 2 diabetes, and also unfortunately even children on autopsy, coronary artery disease has been found and seen in patients with NAFLD. So here's an illustration on how non-alcoholic fatty liver disease increases the risk of cardiovascular disease. Things like endothelial dysfunction, altered lipid metabolism, systemic insulin resistance, oxidative stress, plaque formation, systemic inflammation, all of these things lead to an increased risk of cardiovascular disease and events. The Angulo study is a highly cited study that looked at over 600 patients with NAFLD and it demonstrated that NASH with advanced fibrosis stage is most predictive of liver related events. Both stage of NASH and fibrosis predicted overall mortality. This study also showed that those patients with NASH have an increased risk of mortality due to cardiovascular disease, 38 versus 32 percent in the general population in the U.S. The next objective is assessing risk of cardiovascular disease in patients with NAFLD. Non-alcoholic fatty liver disease and atherosclerotic cardiovascular disease prevention. The first thing is always identify NAFLD. It is important to complete a comprehensive cardiovascular risk assessment, focus on lifestyle modifications, healthy dietary patterns, physical activity, weight loss, limiting alcohol use. Assessing risk for cardiovascular disease. What is recommended is that we use the atherosclerotic cardiovascular disease risk calculation or ASCVD risk. It is the foundation of primary prevention and typically it is used for the ages between 40 and 79 years of age and it calculates a 10-year risk of heart disease or stroke. You see on the right the different questions or things you have to put into the calculator and then it gives you a number to know how to manage the patients and how to approach each patient. You see here is a snapshot or the algorithm and how you manage patients with using this calculation. It is the primary prevention and it assesses the ASCVD risk in each age group and all of it really does emphasize lifestyle modifications, having a healthy lifestyle but it also tells you what to do if they're at intermediate, borderline risk, high risk and also making sure that you consider those ASCVD risk enhancers. Things like family history, chronic kidney disease, metabolic syndrome, you want to use this to guide your, you know, whether you need to refer to cardiology or just really talk about lifestyle modification which we do for NAFLD patients already. Refining risk estimates for individual patients. This slide goes into more detail of what do we do with patients after we calculate that 10-year ASCVD risk, what what do we do next and so you see across the board it's always going to be a discussion about risk enhancing factors and net benefit of therapy. It always is going to involve lifestyle modifications but when you get to borderline risk, intermediate risk, if uncertainty remains, you consider the CAC score and you revise your decision based on the results. In high risk, you automatically talk about lifestyle modification but you also introduce drug therapy. Coronary artery calcification or CAC scoring. This is the best non-invasive predictor of cardiovascular events. It is ordered as a heart CT and I do order this in quite a few of my patients after I do the calculation of the ASCVD risk and if they are at high risk, I do order this test and we have actually found high CAC scores to refer to cardiology to further evaluate these patients. MEZA, multi-ethnic study of atherosclerosis, is a study that looked at CAC scores in Caucasian, African Americans, Chinese and Hispanic Americans to see if there were any differences when you're using the CAC score. They followed over 6,800 people for new cardiovascular events for a median of 3.9 years and what they found is that there were no differences among racial or ethnic groups when using CAC scoring and so when the CAC score is above 300, that's sort of the magic number to say okay we need to refer to cardiology. It yields a hazard ratio of 9.67 versus a CAC score of 0 which the hazard ratio is 1. So coronary artery calcification is increased in NAFLD. There was a study that looked at 1575 Korean participants in a health screening program and over four years they followed these patients. What they found was that 148 subjects with baseline CAC of 0, 9.4 percent, developed coronary artery calcification. An ultrasound diagnosed NAFLD at baseline in 46.6 percent of subjects and the proportion of subjects who developed CAC was significantly higher in subjects with NAFLD at baseline, which you see in the graph at 12.4 percent, versus those without NAFLD at 6.8 percent. And so this shows and demonstrates how when you have NAFLD your CAC score and risk of developing coronary artery disease over time is increased in those patients with non-alcoholic fatty liver disease. Hypertension treatment guidelines. So 2017 hypertension guidelines, the prevalence of high blood pressure, 46 percent of US adults versus 36 percent based on JNC 7 definition. Most people between 130 to 139, over 80 to 89 will not require medication. The classification of blood pressure, it's good to go to review this, is that normal is still less than 120 over 80. Elevated blood pressure is 120 to 129 over less than 80. Stage 1 hypertension is 130 to 139 over 80 to 89. And stage 2 hypertension is greater than 140 over 90. Hypertension guidelines. So here's a snapshot of what's recommended when you manage patients with hypertension or high blood pressure. I have circled the area with stage 1 hypertension and stage 2 hypertension because that's when you want to introduce drug therapy. You want to look at that ASCBD calculation and if it's above 10 percent you want to do non-pharmacologic therapy, but also you want to introduce a blood pressure lowering medication and you reassess in one month. If you have stage 2 hypertension, which is greater than 140 over 90, you want to go ahead, you want to talk about those lifestyle modifications, but you also want to go ahead and introduce antihypertensive medication. And so all categories as you see again, talks about lifestyle modifications, healthy habits, and you want to make sure to educate and take time and discuss that with your patient. So here's the 2017 hypertension guidelines. And when you discuss treating high blood pressure, all patients with blood pressures above normal should be treated with non-pharmacological interventions. And that talks about the heart healthy diet, the DASH diet, reducing sodium intake, potassium supplementation, increasing physical activity, limiting alcohol consumption, and losing weight for those who are overweight. And so all this sounds familiar because that's pretty much what we discuss with our patients dealing with NAFLD. Pharmacological intervention for individuals with stage 1 or 2 hypertension and or high risk of cardiovascular disease. And that's when that ASCVD risk is greater than 10% is when you want to introduce drug therapy. Blood pressure treatment threshold for people with high blood pressure. Adults with confirmed high blood pressure without a history of cardiovascular disease and their ASCVD 10 year risk is less than 10%, you want to introduce a blood pressure lowering medication when their blood pressure is consistently over 140 over 90. Now for adults with clinical cardiovascular disease, you want to start medications when their blood pressure is greater than 130 over 80. And a target close to 120 over 80 is generally better than a higher blood pressure target. So you still want to aggressively treat these patients. Even when they're on medication, you still want them under 120 over 80. Selection of an initial antihypertensive agent. Initial drug therapy can include ACE inhibitor, ARB, calcium channel blocker, or a thiazide diuretic. However, in African American patients, they should be started on either a thiazide or calcium channel blocker. And for those patients with chronic kidney disease, initial therapy should include ACE inhibitor or ARB. Now if the target blood pressure is not reached within one month after initiating therapy, the dosage of the initial medication should be increased or a second medication should be added to make sure you hit that target of less than 120 over 80. Now switching gears to hyperlipidemia treatment guidelines. So this slide is the 2019 ACC AHA guideline on the primary prevention of cardiovascular disease in relation to high blood cholesterol. And so this algorithm looks similar because we're still using the ASCVD calculation and calculating the 10-year risk of cardiovascular disease and stroke. And so you see in the circled area, now we're introducing statins. And so instead of blood pressure lowering agents, we're talking about statin use and when to introduce it. And so you still see the ASCVD risk enhancers. And so that does come into play when you get into the borderline risk. And you have to consider, you know, family history, you know, metabolic syndrome, chronic kidney disease, different things, ethnicity, different things that may play a part into your management in that particular patient. Lifestyle modification is always and should always be discussed. But the introduction or initiation of statin therapy really comes in at the intermediate risk, 7.5% to 20%. And also the high risk patient for cardiovascular events. And if you are still uncertain sort of that gray area, that HEART-CT is still recommended and getting a CAC score to help guide your management of that particular patient. Now this slide, it goes into more detail when it talks about the ASCVD risk. Of course, you still want to have that healthy lifestyle talk. But also, it looks at if they're not at very high risk of ASCVD, their calculation doesn't put them in a high risk category, then you want to look at their age. If they're less than 75 years of age, if they're greater than 75 years of age. However, if they are at very high risk, you do want to do a high intensity statin or maximum statin. And you want to get to that point to aggressively get that LDL down. And so that prevents them from having their first cardiovascular event. And so here are the high, moderate and low intensity statin therapies. And you see that a lot of it is dealing with dosing. Of course, the moderate intensity has the most medications. And there's plenty of options of one doesn't work, doesn't work, or they have side effects or other things we can offer patients. High intensity is when you really want to get those patients down, and their LDL greater than 50%. And those are those high risk patients that when you do that calculation for the ASCVD risk assessment, and then low intensity. I'm always about go low, go slow, as we all have learned. But these are the categories when you see that with the algorithm. Non-alcoholic liver disease and statins. So this is an ongoing conversation. Statins are still underutilized in patients with liver disease. There's always that worry that, oh, gosh, they're going to have liver issues or complications, or I'm going to cause more problems. And that's just not the case. Significant hepatic injury is extremely rare. And so those patients need a statin. They absolutely should be prescribed a statin. And you will continue to monitor patients as you would who don't have liver disease. Because we know, as we've talked about, cardiovascular disease is the leading cause of complications for NAFLD patients. So they absolutely should be prescribed statins if it's indicated. Patients with NAFLD and elevated liver transaminases are not at increased risk of complications or problems. And so potential to improve NAFLD, we don't know that yet. We don't have enough data or enough studies or anything to say that for sure, reduction in cardiovascular events. There's ongoing studies to show that as well. But we do know that if a patient needs statins, it is safe for a patient with liver disease to take statins if it's indicated. And so today's take-home points that NAFLD and cardiovascular disease share numerous risk factors. Both are manifestations of end organ damage of metabolic syndrome. NAFLD may independently increase risk of cardiovascular-related complications. Further investigation is needed regarding pathophysiologic mechanisms, tools for risk assessment, and treatment approaches. And current cardiovascular recommendations specifically for NASH patients are limited. I thank you so much for your time. Welcome to Identification and Initial Treatment of Type 2 Diabetes in NAFLD and NASH. My name is Dawn Piercy. I'm a nurse practitioner at Duke University Medical Center where I've worked for the last 16 years. I work in the Division of Gastroenterology and Hepatology in a specialty NASH clinic. I also serve as a sub-investigator on NASH clinical drug trials. For that reason, I have these disclosures, but none of these are pertinent to today's presentation. Hi, everyone. My name's Katherine Cryer. I'm an associate clinical professor at Duke University School of Nursing. And I am the lead faculty for the endocrinology specialty training program there. And I also practice in adult endocrinology at Duke University Medical Center. And I'm happy to be with you today. And I have no disclosures. So let's start off by discussing why it's important for us to know whether or not our patients have prediabetes or diabetes when they have NAFLD, especially since we work in a GI or hepatology practice. Remember that one of the important things in assessing our patients with NAFLD is understanding whether or not they're at risk for progressive liver disease. And to ascertain that, we have to really get a good look at all of their risk factors. Literature shows that type 2 diabetes mellitus being present in those with NAFLD increases the risk for more advanced NAFLD and its associated complications, including liver decompensation and the need for liver transplantation. NAFLD patients with type 2 diabetes have increased mortality, not just from liver disease, but from all causes. We also know that HCC is more common in those with type 2 diabetes and NAFLD. And those that have NAFLD that don't have diabetes yet are at risk of developing diabetes at some point in the future. Diabetes and NAFLD is really common. Earlier in this session, you heard Anthony talk about how common NAFLD is around the world, but it's even more common in certain populations. Dr. Yannasi and colleagues have shown that in type 2 diabetic populations, the prevalence of NAFLD is around 55%. In the same population, NASH is prevalent at about 37%, and 17% of patients with type 2 diabetes have the more advanced forms of NASH with advanced fibrosis. The incidence of type 2 diabetes has also been looked at by Dr. Yamazaki and colleagues, and they found that type 2 diabetes is more commonly found in those with NAFLD as opposed to those that don't have fatty liver disease. It kind of makes sense that diabetes and fatty liver disease are related when you look at the pathophysiology of NAFLD. It used to be thought that this was just a two-hit process that led to progression of this disease, the first hit being related to a combination of genetics, poor diet, excess weight, leading to increased circulation of free fatty acids, further leading to fat deposition in the liver cells. And then this made the liver more susceptible to oxidative stressors, leading further to fibrosis of the liver. We now know that this is a much more complex issue, that there are multiple organs and multiple insults that are taking place when fatty liver disease develops. Some of the organs involved include adipose tissue, which releases lipids and cytokines, leading to further insulin resistance. We know that the intestinal microbiota of type 2 diabetics with NAFLD is different than those without these conditions, and it's probably related to the underlying pathophysiology of NAFLD. When skeletal muscle is affected by free fatty acids, there's increased lipid deposition, and then the muscle becomes more insulin resistant. And as the liver becomes more insulin resistant, more glucose is produced, causing the pancreas to release excess amounts of insulin. So, as practitioners, we always enjoy having guidelines that help to guide our practice. And there are specific clinical guidelines for GI and liver specialists. This one is from the AASLD and was published in 2018, stating that the management of NAFLD should consist of treating the liver disease, but also treating the comorbidities that are related, and diabetes is one of them. Another clinical practice guideline that was published by both the European Association for the Study of the Liver, the European Association for the Study of Diabetes, and the European Association for the Study of Obesity tells us that all individuals with steatosis should be screened for features of metabolic syndrome. And they even take it a step further, saying that people with NAFLD should be screened for diabetes, and this is mandatory. So, we're going to talk a little bit more about screening for diabetes, and this is mandatory. The World Gastroenterology Organization also published a guideline stating that in the absence of treatment specifically for NASH, we should be treating the associated comorbidities that underlie NAFLD and NASH, and that includes diabetes. And for all practitioners, the American Diabetes Association has published the Standards of Care for Diabetics in 2020. This is telling us that testing for prediabetes and type 2 diabetes in asymptomatic adults with obesity or just even overweight, and having one or more additional risk factors for type 2 diabetes should be taking place. And they also recommend that we consider testing adults for diabetes starting at the age of 45. So, now we're going to talk about the criteria for the diagnosis of diabetes, and this is for the patient that you see in your clinic and they have not previously been told that they have diabetes. So, just keep an eye out on your lab work. So, we know that a fasting plasma glucose of over 126 is diagnostic for diabetes, and you want to make sure that they have been fasting for at least eight hours prior to that. So, no coffee, no creamer, et cetera, no sugar prior to the lab test. The second one I'll point your attention to is the A1C test, which is probably the most easy and practical to do in the clinic setting. And an A1C of over 6.5% is diagnostic for diabetes. And then the last one I'll point your attention to is the random glucose in combination with signs and symptoms of hyperglycemia. So, if someone has a random glucose at any time of day, and they're also having polyuria, polydipsia, polyphagia, they're losing weight, they're not feeling well, then that random glucose can be diagnostic. And it's important to note that you have to do at least two different tests in order to confirm diabetes. So, if you get one A1C level of 6.6%, you can't diagnose them with diabetes quite yet, you have to do a second confirmatory test. And the confirmatory test can be either from the same sample or it can be in two separate test samples. It's also important to note what the criteria is for pre-diabetes because these patients are at high risk for eventually developing cardiovascular disease and eventually converting to diabetes. And so, you wanna be on the lookout for those who have a fasting plasma glucose between 100 and 125. Basically, anything over 100 is abnormal, so that's easy to remember. And then the A1C between 5.7 and 6.4 is the other one to keep an eye on. And I'm not pointing your attention to these oral glucose tolerance test features that diagnose this because these are not very practical to do in your liver clinic setting. It's something you'd see more in OBGYN and endocrinology, sometimes in primary care. So, I think the fasting random and A1C are the easiest ways to diagnose diabetes. It's important to think of what the A1C goals are for our patients. So, for most non-pregnant adults, an A1C less than seven is appropriate. Now, if you have someone who is recently diagnosed with diabetes, they're not yet on any medication, they're not at high risk for hypoglycemia, then an A1C six and a half or less may be a very reasonable goal for them. So, this has to be tailored to a degree, but for most patients, the A1C less than seven is going to be our target. The foundation of all diabetes management is lifestyle. And this is no secret to any of you, but some of these goals that line up with diabetes also are things that I know that you do for fatty liver disease. So, just a couple of points here. The first is that there is no specific eating pattern that is recommended for type two diabetes. And that's because everyone is individualizing therapy now, that's what's recommended. And so, we don't say everyone should eat a Mediterranean diet. We just want patients to lose weight and we want them to eat a well-rounded nutritious diet. So, the first goal should be achieving at least a 5% weight loss. And I know that that lines up with some of the fatty liver recommendations that we'll talk about in just a few minutes. Also, really limiting sugary beverages, right? That should be one of the first things we cut out. And then of course, focusing on nutrient dense carbohydrates. So, really trying to eliminate breads, pasta, potatoes, rice, all of the white items and focusing on nutritious whole foods. As far as physical activity, again, these are fairly similar to your NAFLD recommendations. The American Diabetes Association recommends 150 minutes or more of moderate to vigorous intensity activity. And then some resistance exercise, at least two to three sessions a week. And then the bottom line really is decreasing the amount of time that someone is sitting. So, really trying to have them be more active, even if it's not true physical activity or exercise. So, the effect of lifestyle on NAFLD and type two diabetes. So, there's available evidence suggesting that just increasing your physical activity and lowering your calorie intake can really reduce intrahepatic triglycerols. That's a hard one to say, isn't it? And which is similar to a triglyceride essentially. And that will also in turn, improve glycemic control and insulin sensitivity. And this is for patients in both NAFLD and type two diabetes. And so, that's no surprise to any of us. But I think if we're really trying to break it down and think about what we need to do is having patients move more and eat less, right? And the other thing is that any kind of exercise has really been shown to be beneficial for these patients with both comorbidities. And so, that can even be helpful independent of body weight changes. So, they don't even necessarily have to lose weight. We want them just to move and be more active. So, it looks like from available data that seven to 10% weight loss is required to observe beneficial effects on the NAFLD parameters. And remember I said 5% for diabetes parameters, such as insulin resistance and glycemic control. But it looks like also that about three to 5% weight loss may be beneficial in patients with NAFLD who do not have obesity. So, there may be some individualization here as far as what we're looking for to improve outcomes. Metformin is the preferred initial pharmacologic agent for the treatment of type two diabetes. And this is based on all of the current guidelines that are published. This has been the case for a long, long time. Metformin came out in 1995. So, maybe it's not quite that long, right? But we still use metformin all the time for most patients with diabetes as initial treatment. And in general, we think of metformin being additive. So, once patients are on metformin, they usually stay on it and then we add from there because we know especially that it helps with insulin resistance and it's a very inexpensive and effective treatment for diabetes. As far as metformin data and NAFLD and HCC. So, there are multiple clinical trials supporting the benefit in NAFLD patients with improvement in biochemistry. So, we're looking at liver enzymes, right? And then metabolic syndrome features such as BMI and weight. And the effect on liver histology specifically remains controversial. So, there's not a blanket statement saying that metformin is this miracle drug, but we do know that it can be beneficial in these patients. There's also some interesting data showing that metformin may reduce the risk of developing HCC in patients with type 2 diabetes, and it may also improve survival in the patients who actually already have HCC. So, I think there's enough data here. And the second bullet point actually is based on a systematic review and meta-analysis of hundreds of thousands of patients. So, we're talking about the prevention of HCC. And then the third bullet point is based on a systematic review and meta-analysis of over 3,000 patients with liver cancer. So, I think this data is very reassuring, and especially in line of the fact that metformin is very safe, then this is a great option. Here are some metformin prescribing tips if you're someone that's interested in metformin in the future. A lot of this is not a surprise. I think the one thing to keep an eye on are the renal dose adjustments. And these were recently changed in 2016 by the FDA. So, now we're able to use metformin more in patients who have a lower GFR level, which really opened up the doors for more patients to be able to use this medicine. So, you just wanna keep an eye on the GFR as far as what the thresholds are. One tip that I'll mention to you is that if someone is complaining of GI side effects with the metformin, switch them to extended release, because a lot of times they will do much better with extended release, and they won't have these side effects. There is other data that's really interesting about other medications in diabetes that have improvements in patients with fatty liver disease. And you may have heard of pioglitazone and rosiglitazone, right? And the thiazolidinediones are one that have had some interesting data related to the outcomes in fatty liver disease. And we really don't use pioglitazone anymore because it can cause some significant issues related to heart failure and edema. And so, it really has fallen out of favor, particularly with endocrinologists. It is used sometimes in small doses for certain patients, but we really don't use it a lot. So, there was some just challenges with that medication related to weight gain too. And so, unfortunately, because it did have some good data related to fatty liver disease, but we're really shying away from that now. The newer medications, such as the GLP-1 receptor agonist, as well as SGLT-2 and DPP-4s, have also been shown to improve liver enzymes and liver fat content. So, that is all very promising. And those are medicines that would never be expected for you to prescribe within the context of your liver clinic. If you're someone who loves diabetes, you could really get into that and find out more and learn how to do additive and stepwise therapy and so forth, because there is some really interesting data on how those can affect patients with liver disease. In general, though, the bottom line is to really try to select medications that are weight neutral or that will contribute to weight loss. And so, at this point, most diabetes medications, the ones that cause weight gain are insulin and sulfonylureas are the two most common. So, you really want to try to stay away from those. If you can, some patients really need insulin. So, our key takeaways are that NAFLD and type 2 diabetes are very common and closely associated with each other. Incident type 2 diabetes occurs more often in NAFLD patients compared to those without NAFLD. There are multiple guidelines to support screening and management of prediabetes and diabetes in NAFLD patients. The pathophysiology of NAFLD and type 2 diabetes is closely related to insulin resistance. And for diagnosis, you can use A1C or random glucosis to diagnose, but you do need two tests in order to confirm. You want to counsel all your patients on diet and lifestyle adjustments. You'll start most patients on metformin who have diabetes if they're not already taking it. And then multiple classes of diabetes medications have shown improvement in NASH and NAFLD. Thank you. And now, on behalf of Dawn and myself, we'll be happy to take questions during the session. Thank you for joining us today in the Associates 6 programming. I'd like to thank my co-chair, Tiffany Kaiser, and I'm Vicki Shaw. And if you have any questions, go ahead and type them in the chat box. Our presenters are available to answer any of the questions you may have. Also to note, we do have some associate events coming up, which include the Associates Lounge with ongoing conversations and the Associates course tomorrow, Sunday. We hope for you to join us. Thank you.

Liver Meeting 2020

Hepatology Associates SIG

metabolic syndrome

NAFLD

NASH

diagnosis

treatment

cardiovascular risk

lifestyle modifications

pharmacological agents

NASH treatment