Hello, and welcome to this ASLD guideline update. I am Andrew Keefney, I'm chair of the ASLD Online Learning Committee, and it gives me great pleasure today to introduce Dr. Richard Sturdy, who's Professor of Medicine and Chief of the Section of Hepatology at Virginia Commonwealth University, as well as the Chief Clinical Officer of the Stravitz-Saniel Institute for Liver Disease and Metabolic Health. And also, and importantly, he is the lead author of the new ASLD clinical practice guidelines that we're going to discuss today. And these guidelines are on blood-based, non-invasive liver disease assessments of hepatic fibrosis and steatosis. Dr. Sturdy, many thanks for joining me today. Dr. Sturdy presented an update on these guidelines at DDW 2024. And really what we'd like to do today is just discuss the highlights of his presentation. So Dr. Sturdy, again, thank you for joining me today. Welcome to liver learning. So what was the background for developing these new practice guidelines, Dr. Sturdy? Yes, good afternoon. So the understanding of fibrosis stage is really paramount to managing those with chronic liver disease or CLD. It not only can provide prognostic information, but also identifies those who are at risk for developing complications of cirrhosis, such as portal hypertension, ascites, hepatic encephalopathy, and variceal bleeding, and identify those at risk for developing hepatocellular carcinoma, or HCC. Additionally, fibrosis stage is often considered when determining if treatment is indicated, such as those with viral hepatitis or those with metabolic dysfunction associated steatotic liver disease, now called MASL-D. The gold standard for fibrosis assessment had been liver biopsy. However, we know that liver biopsy and invasive procedure can be associated with bleeding, pain, and rarely puncture of other organs. It's also the subject of sampling error. Liver biopsy, however, is still needed in certain situations, such as those in autoimmune hepatitis to determine if it's safe to stop all immune suppression, in those with MASH to determine if treatment is indicated, and often post-transplant to rule out rejection. However, I've always said that the only things worse than doing a liver biopsy is either having one done on yourself or teaching someone else how to do a liver biopsy. So as such, over 30 non-invasive tests have been developed, and over the last 10 years, in most situations, non-invasive liver disease assessments, or NILDA, has replaced liver biopsy in clinical practice. There have been almost 10,000 studies and reviews on non-invasive tests for liver disease severity in the last 20 years. And the purpose of these guidelines was to review the literature through April of 2022 and provide an evidence-based approach on their use. Thank you for that. In your opinion, what are the key changes in practice that are presented in these new guidelines? We know that NILDA is categorized as either blood-based or imaging-based, and they're often used either alone in combination. Blood-based NILDA can be further divided into simple, non-proprietary tests, such as the AST to Platelet Ratio Index, or APRI, the Fibrosis 4 Index, or FIB4, and the NAFLD Fibrosis Score, or NFS. And then we have more complex proprietary models that include direct markers of fibrosis formation or degradation. Most of the imaging-based NILDA uses elastography for liver stiffness measurement, or LSM, for fibrosis, or an attenuated parameter for steatosis. The ASLD brought together a group of experts, including myself, that included both adult and pediatric pathologists, radiologists, and pathologists, and we identified key clinical questions to address the use of both blood- and imaging-based NILDA to identify fibrosis steatosis. And what we're not going to talk about today is clinically significant portal hypertension. Working with the Mayo Clinical Evidence-Based Practice Center, we developed three guidelines using the Patient, Intervention, Comparison, and Outcome, or PICO, approach, and three accompanying systematic reviews, one for each of the guidelines. When the evidence from the systematic review was not there for a guideline statement, ungraded guidance statements were developed. And for each statement, regardless, technical remarks were included to provide the clinician with context. Our writing group also worked with several other ASLD guidelines and guidance groups, such as the autoimmune hepatitis group, the Masl guidelines group, and the portal hypertension group, to have consistent message and to avoid contradictory recommendations. So the key changes that we recommend is that clinicians should really start with simple, non-proprietary tests over the more complex tests, since, based on our systematic review, the simple tests like APRE, FIV4, and NFS work almost or just as well and are essentially free. We also state that these tests work best before treatment is started, as any changes after treatment may reflect improvements in inflammation rather than fibrosis. Most of the NILDA was developed, however, to identify those with bridging fibrosis or cirrhosis, which we termed advanced fibrosis, and not really to identify those with at least F2 or greater, termed significant fibrosis. We also recommend that for those with blood-based NILDA tests above the lower threshold that they go on to have an imaging-based NILDA test. And given the cost and availability, most of these imaging-based NILDA will be ultrasound-based elastography. Overall, we have found that all NILDA work better to rule out advanced fibrosis at the lower threshold than to rule it in at the upper thresholds. We also found that imaging-based NILDA should be used to identify steatosis, as the blood-based models did not perform that well when compared to either liver histology or MRI-based tests for steatosis. We also recognize that there are limitations of all NILDA and that they really need to be interpreted in the clinical context of the patient and any comorbidities that may impact labs that do not reflect hepatic fibrosis. For example, any age-based NILDA, such as FIB4, will not work as well when they're very young or old. The guidelines provide details of all the situations that might impact the performance of each test. How should we apply these guidelines in practice? So we really tried to put the patient as the focus for our guidelines. And in an effort to facilitate incorporation of NILDA into clinical practice, mostly again for adults, the ASLD NILDA writing group developed an algorithm intended to be used by clinicians in the need of readily available simple decision support tools to identify those with both significant and advanced fibrosis. And for the clinician, it starts with a simple blood-based NILDA test, such as the APRE and FIB4. And for MASL, you can use either the FIB4 or the NFS. For those below the threshold, especially if more than one test agrees, the chance that that patient has advanced fibrosis is very, very low. For those above the threshold with a blood-based test, we then recommend an imaging-based NILDA test be performed, again, typically elastography. If the result is above the upper threshold, then that patient may have advanced fibrosis, while those in between the lower and the upper cutoffs require closer follow-up or additional testing. Rarely, liver biopsy then may still be needed. It's important, however, to recognize that while the sensitivity and specificity of each test have been defined, the positive and negative predictive values will depend on the population. Therefore, a NILDA may work differently in a primary care or general population where the prevalence of advanced fibrosis is low, let's say under 5%, compared to a referral hepatology practice where the prevalence of advanced fibrosis may be greater than 30%. If the question is, does my patient have steatosis, then we found that imaging-based NILDA, such as the attenuated parameter, is the test to do because blood-based NILDA is not accurate enough. And the data in pediatric patients we found is much less robust, but we did find that NILDA can be used in pediatric patients with chronic liver disease. Are there any particular patient groups that we should focus on using NILDA? Well, for most of us clinicians, the most common diseases we see are viral hepatitis, measles, and alcohol-related liver disease. While the ASLD systematic review identified sufficient data for chronic untreated hep C, hepatitis B, and measles D, there were far fewer studies for other diseases, such as primary biliary cholangitis, primary sclerosine cholangitis, hemochromatosis, and alcohol-related liver disease. And remember, for those with viral hepatitis, it's important to use any NILDA prior to initiating treatment, as most improvements in NILDA after treatment may be related to decreases in inflammation and not in fibrosis. We also did not find sufficient evidence to use blood or imaging-based NILDA over time to assess fibrosis progression or regression. However, I have found in my practice that imaging-based NILDA to monitor steatosis after weight loss has been helpful. Also, we identified several areas for future research. Would you like to elaborate on the areas of research that we should focus on going forward? Sure. So we definitely think that NILDA needs to be studied more in marginalized populations, needs to be studied more in primary care populations, where often those studies have not had liver biopsy as the gold standard, so that may still remain a challenge. We think that AI is becoming important, and there have been some studies and there are other tests emerging out there that use AI-based or machine learning technology to help include more factors within to try to better identify patients. And certainly, there's emerging data on using more metabolites and metabolomics to help do more specialized testing, particularly if trying to identify patients, for example, with treatable MASH, the F2 in greater patients that are currently being where some of the newer drugs are going to be effective. Well, I think we can look forward to learning about these new developments and seeing them in the future updates in the guidelines. But for now, I'd really like to thank Dr. Stirling for joining us. If you would like to learn more about this topic, you're very welcome to access his talk on liver learning that was presented at DDW 2024 and read the guidelines themselves, which are published in hepatology. Thank you again for joining us. I would encourage you to complete the online evaluation of this activity. Your feedback will help us to plan new educational offerings that will meet your needs. You can also share comments with us about this course or any of the other liver learning programs by clicking the feedback button on the liver learning homepage. Thank you very much.

Hepatology

non-invasive tests

liver disease

fibrosis assessment

ASLD guidelines