Our first lecture is going to be on something that we're seeing a lot with, you know, we have an epidemic of NASH and NAFLD and with that comes fibrosis and cirrhosis. And Phoenix is going to talk to us about the endoscopic assessment of advanced liver fibrosis. Phoenix, thank you very much and welcome. Thank you so much. It's such an honor to be here today. I'm just really thrilled to talk about this topic of endohepatology. I have no disclosures and just going to jump right into it. So I think EUS has evolved very rapidly over the years and now it's found a particular niche in hepatology and now it's coined endohepatology. I'm going to focus on diagnostics as there's a whole therapeutic arm for endohepatology and I think it's great timing with the increasing problem, as John just noted, with liver diseases in the rising obesity epidemic. When I talk to a referring physician for endohepatology, I think of five different components. For years now, we evaluate patients with EUS coming in with elevated liver tests and we can look at the bile duct, the gallbladder, pancreas, and endoscopically, you can evaluate, of course, for esophageal varices, but using EUS, you can look at the adjacent area to the esophagus and look for paraesophageal collaterals that can't be seen on endoscopy. Over the years, then, we went in to be able to provide that one-stop shopping and we can do EUS-guided liver biopsy, which I'm going to detail today. And then in the recent years, there's development of EUS-guided portal pressure gradient measurement or PPG, which I will outline a little bit and then Dr. Shiraiha will give you the details. We also have, as number five, EUS-guided shear wave assessment, which can simulate what we do with the FibroScan. So those are my five components and so what is the role of a liver biopsy? I think to give you a little bit really brief on the background, it is a gold standard in evaluation and management of patients with liver disease. I think we know that and I think it's used to diagnose complex liver diseases that cannot be diagnosed with blood tests and imaging studies. For example, differentiation between drug-induced liver injury and autoimmune hepatitis, those two can often overlap. Differentiation between NASH and NAFLD diagnosis of PBC and NASH may often require a liver biopsy for histologic diagnosis. Liver biopsy can be used to stage or estimate the degree of liver damage. Fibrosis and cirrhosis can sometimes be missed up to 30% of the patients without a liver biopsy. The AASLD in 2018 came up with a recommendation. It suggested that liver biopsy be considered in patients with higher risk of fibrosis with non-invasive imaging measures or in patients with metabolic syndrome where advanced disease is suspected. A little bit about fibrosis, very briefly, I think it's the hallmark of liver damage and it's the most important predictor of outcomes in patients with underlying liver disease. I think that's known. Historically, the severity of fibrosis is defined by a percutaneous liver biopsy and now it's replaced by laboratory and imaging techniques that are non-invasive markers of fibrosis. These things are helpful when you have advanced fibrosis, but it can be limited in patients with intermediate amounts of liver damage. I think the FibroScan may be limited in patients with higher BMI and in patients with mild to moderate disease. Okay, conventional liver biopsy is the percutaneous route as we talked about CT or ultrasound guided. It can be complicated with pain, hemorrhage, and transjugular liver biopsy is an alternative that is thought to be safer particularly in patients where you have massive ascites, obesity, or coagulopathy. However, it still has high complication rates and it needs fluoroscopy. Of course, we're going to jump into EUS guided liver biopsy. Due to its vicinity to the liver, endoscopic ultrasound can directly biopsy under visualization of ultrasound and we can do it EUS guided with less adverse events. Studies show that EUS liver biopsy is safe, it's efficacious, and it provides excellent histologic specimen and that's key take-home message. I think the real-time liver biopsy by EUS avoids accidental injury to vessels and organs that are adjacent to the liver and patients with the percutaneous approach can have subcapsular bleeding and they can have pain. That's not what we see with EUS. EUS liver biopsy I think provides diagnosis regardless of fibrosis score. There's been studies out there comparing different types of needles and when we look at the one study that compares the Francine tip, which is the three-pronged tip by Boston versus the fork tip, which is a shark core needle, they have very similar adverse events. Comparison diagnostic accuracy, I think the Francine came out with higher accuracy. Typically we talk about how many passes we do, how many actuations with each pass. There's a description of this wet suction technique. The wet suction is where we prime the needle with a little heparin and we leave the heparin in the needle and that allows for that capillary action and then we apply suction that the needle handle and it provides really excellent portal tracks for diagnosis. Different societies have recommended for adequacy in liver biopsy EUS guided and we'd like 11 or more complete portal triads and greater than 25 centimeters on length of the core on the biopsy. Advantages, EUS guided, we can sample both left and right portion of the liver. So for patients with more diffuse disease, whereas the percutaneous technique, you get only the right side. It's typically an outpatient procedure, discharged within an hour. I haven't had any problems with delayed bleeding and it can be done at the same time that you do biliary evaluation. For outcomes, there's a meta-analysis of the 23 studies and more than the recommended length of specimen was noted with more than the recommended complete portal triads noted, high yield and very minimal adverse events. So to wrap this up, so I told you what it is, why we do EUS guided liver biopsy and a little bit about how we do it. I think it's safe and quite effective. It's easy to perform in experienced hands and I think as an endosynographer, we'll be able to do this with a not so long a learning curve. It's useful, I think, if we're going to do EGD or EUS for other indications and nice to combine this technology with PPG. So a few years ago, with Dr. Ken Cheng, I reported the first series early in the infancy of EUS on EUS guided FNA of liver lesions and we thought, wow, that was genius. And then fast forward now, we're doing core liver biopsy and Dr. Cheng came back to the liver and created what we now know as EUS guided PPG. So I'm just going to outline a little briefly about what PPG is and then I'll hand it over to Dr. Shahraiya. Portal hypertension I think is a serious complication of cirrhosis and the hepatic venous pressure gradient accurately reflects the degree of portal hypertension. And the HVPG can predict clinical decompensation in cirrhotics, predict the development of cancer in the liver, predict survival. So I think this is an important parameter. HVPG is measured currently by interventional radiology with a transjugular technique. However, it's invasive, has some radiation, and it's really an indirect measurement. With the EUS guided technique, EUS guided PPG, it was initially done on animal models and then human studies using a 25-gauge FNA needle with heparinized saline and a compact manometer that gives you a digital readout, fabulous innovation. And EUS PPG was shown to correlate statistically with clinical parameters of portal hypertension. This is a little bit about the how we do it, EUS guided PPG. To the right you see our device. It's a 25-gauge needle connected to a manometer and the handle looks very similar to an FNA handle. We usually do this with patient in supine position, they're sedated. And in my practice, and I think in most practices, we do this prior to the liver biopsy, that one-stop shopping. So initially we do three consecutive measurements of the hepatic vein over 30 seconds and we take the mean of those numbers and then we repeat the process in the portal vein to obtain pressures. We take the difference of the mean and you have that gradient. So I'm going to hand this over to Dr. Sharaya to talk to you more in detail about PPG.

endoscopic ultrasound

liver fibrosis

EUS-guided liver biopsy

portal pressure gradient measurement

endohepatology