The term "endohepatology" was coined over the last 15 years to describe the integration of interventional endoscopy and hepatology for the management of patients with chronic liver disease. In this article, we will review the diagnostic and therapeutic applications of endoscopic ultrasound and endoscopic retrograde cholangiopancreatography among liver transplantation candidates and recipients.

With the rapid development of endoscopic ultrasound (EUS), diagnostic and therapeutic platforms have emerged that are applicable in hepatology. New tools such as EUS-guided portal pressure measurement (in combination with EUS-guided liver biopsy) or EUS-guided variceal obliteration using coils and glue present attractive procedures that can potentially overcome the limitations of current gold standards. In this review article, we provide an overview of these new 'endo-hepatology' techniques and highlight their current role in the treatment of liver diseases.

Over the past several years, there has been increasing interaction between Hepatology and Endoscopy, mainly facilitated by EUS-guided modalities. There are 4 main areas that have led to the emergence of what has been called "Endohepatology". The first is EUS-guided parenchymal liver biopsy (EUS-LB). An optimal technique EUS-LB has been developed using a 19G EUS fine needle biopsy needle with "wet suction." There are several advantages to EUS-LB. Another component of Endohepatology is the ability to directly measuring portal pressure gradient (PPG) under EUS guidance. A 25G needle can be inserted directly into branches of the hepatic vein and portal vein to measure PPG. Although this technique requires a sedated endoscopic procedure, it is technically easier and better tolerated than the traditional transjugular approach and is very safe. Newer techniques of endoscopic management of gastric varices using EUS-guided injection of glues and coils is another driver of Endohepatology. EUS-guided glue injection is safer than direct endoscopic injection, and the use of coils decreases the incidence of glue embolization. The fourth pillar is expanded use of EUS-guided gallbladder drainage (EUS-GB) with lumen apposing metal stents. This is beginning to revolutionize management of gallbladder disease in cirrhotic patients who are poor candidates for cholecystectomy. Endohepatology will grow as these 4 main applications become more widespread and Hepatologists become more comfortable with the role of Endohepatology in patient management.

EUS-guided portal pressure gradient (EUS-PPG) measurement has been proposed as a novel direct manometry to quantify portal hypertension. This study aimed to explore the ability of EUS-PPG measurements to evaluate the severity of portal hypertension.

The clinical features of patients with diagnosed cirrhosis or chronic liver disease who underwent EUS-PPG measurement at a single center were retrospectively analyzed. The correlations between the clinical features of portal hypertension and the EUS-PPG measurements were analyzed, and then receiver operating characteristic curves were used to evaluate the ability of the EUS-PPG measurements to evaluate disease severity.

A total of 197 patients were included in this study. The EUS-PPG measurements varied significantly among patients categorized by gastroesophageal varices, red signs, variceal bleeding, ascites, hepatic encephalopathy, thrombocytopenia, hypoproteinemia, prothrombin time, international normalized ratio, or Child-Pugh grade (P < 0.05). The areas under the receiver operating characteristic curves for gastroesophageal varices, decompensated cirrhosis, ascites, and recent variceal bleeding were 0.919, 0.847, 0.813, and 0.804, respectively (P < 0.001). Furthermore, the optimal EUS-PPG cutoff values for gastroesophageal varices, decompensated cirrhosis, ascites, and recent variceal bleeding were 11.5 mm Hg (sensitivity = 80.3%, specificity = 89.5%), 12.75 mm Hg (sensitivity = 77.8%, specificity = 76.7%), 15.75 mm Hg (sensitivity = 66.7%, specificity = 83.1%), and 16.75 mm Hg (sensitivity = 76.2%, specificity = 70.1%), respectively.

EUS-PPG measurement seems to be an effective technique for assessing disease severity and risk of variceal bleeding in patients with diagnosed cirrhosis or chronic liver disease.

The armamentarium of 'Endo-hepatology' is proliferating with the advancements in techniques and availability of new devices in the field of endoscopic ultrasound (EUS). This has resulted in the merger of multitude of diagnostic and therapeutic interventions, such as EUS-liver biopsy (LB), EUS-angioembolization of gastric varices, EUS-portal pressure gradient (PPG) measurement, and others into a 'one-stop-shop' for efficient patient management. Lack of standardization of these techniques forms a major hinderance in their widespread adoption.

A comprehensive literature search was undertaken across various databases on EUS-LB and EUS-PPG till November 2024 for reviews, observational studies, and randomized trials on EUS-LB and EUS-PPG, describing its indications, technique, and data of safety and efficacy, detailing its role in day-to-day clinical practice.

EUS-LB and EUS-PPG have shown promise in the ever-growing field of endo-hepatology. EUS-LB has exhibited excellent safety profile and comparable tissue yield compared to its percutaneous counterpart. On the other hand, EUS-PPG seems to be a viable alternative although it needs to be standardized further. From a patient and hospital perspective, they might prove to be convenient and cost-effective. Nevertheless, more evidence is warranted before they can be labeled as the new standard of care.

Percutaneous liver biopsy (PC-LB) has long been the usual method for acquisition of liver tissue. Recently, endoscopic ultrasound-guided liver biopsy (EUS-LB) has gained popularity as an alternative modality. We aimed to compare the efficacy and safety of EUS-LB versus PC-LB.

We systematically searched PubMed, Embase, and the Cochrane Library databases for randomized controlled trials (RCTs) comparing EUS-LB with PC-LB published until October 20, 2023. The primary outcome was diagnostic adequacy. Secondary outcomes were: the number of complete portal tracts (CPTs), longest sample length (LSL), total sample length (TSL), post-procedure pain scores, and adverse events (AEs), including overall AEs and AEs excluding minor post-procedure symptoms. We compared binary outcomes using risk ratios (RRs) and continuous outcomes using the mean difference (MD) or standardized mean difference (SMD), with 95%CIs.

Four RCTs (258 patients) were included. The EUS-LB group presented lower post-procedure pain scores (SMD -0.58, 95%CI -0.95 to -0.22) than the PC-LB group. Both groups performed similarly in terms of diagnostic adequacy (RR 1.0, 95%CI 0.96 to 1.04), number of CPTs (MD 2.57, 95%CI -4.09 to 9.22), LSL (MD -2.91 mm, 95%CI -5.86 to 0.03), TSL (MD 4.16 mm, 95%CI -10.12 to 18.45), overall AEs (RR 0.54, 95%CI 0.20 to 1.46), and AEs excluding minor post-procedure symptoms (RR 1.65, 95%CI 0.21 to 13.02).

This meta-analysis suggests that EUS-LB is as safe and effective as PC-LB and is associated with lower post-procedure pain scores.Registration on PROSPERO: CRD42023469469.

Direct measurement of portal venous pressure (PVP) is invasive, so the hepatic venous pressure gradient (HVPG) is commonly measured to evaluate portal hypertension (PH). HVPG is the gold standard for estimating PVP but few reports have covered standardized measurement techniques.

This study validated standardized techniques for PVP measurement.

In Western countries, electronic transducers are commonly used to measure PVP, whereas the water column method is still frequently applied in Japan. Setting a reference point for accurate PVP measurement is important but complicated. According to Japanese guidelines, the reference point for PVP measurement is 10 cm above the dorsal surface or in the midaxillary line. For simpler determination, the anterior axillary point, defined as the point of convergence between the proximal pectoralis major muscle and arm when both arms are positioned against the trunk in a supine position, can be used as the reference point. New methods, such as endoscopic ultrasound-guided portal pressure gradient, offer less invasive alternatives. Non-invasive methods like elastography measure liver and spleen stiffness, which correlate with HVPG. The Baveno VII criteria incorporate measurements of liver and splenic stiffness for risk stratification. Biomarkers such as type IV collagen, M2BPGi, and FIB-4 score also predict HVPG. The Baveno VII consensus emphasizes the status of HVPG as the gold standard while advocating for non-invasive alternative methods to improve patient care and monitor treatment efficacy.

Continued development of non-invasive tests is crucial for safer, more convenient PH management.

With the recent development of interventional endoscopic ultrasound (EUS), EUS-guided vascular interventions have seen increased clinical and research focus. This modality can be used to diagnose portal hypertension and treat portal hypertension-related gastrointestinal varices and refractory gastrointestinal hemorrhage, including pseudoaneurysm. The vascular embolic materials used for treatment include tissue adhesives (cyanoacrylates), sclerosants, thrombin, and vascular embolic coils, all of which are associated with favorable results. The feasibility of EUS-guided procedures, including portal vein stenting and portosystemic shunt formation conventionally performed percutaneously and transvenously, has also been demonstrated, albeit in animal studies. As EUS-guided vascular intervention is a technique that may receive significant attention in the future, we provide a thorough review of the current evidence for its use.

The last two decades have seen the emergence of endoscopic technologies and techniques allowing for minimally invasive modalities for assessing and sampling lesions inside and outside of the gastrointestinal lumen, including the chest, abdomen, and pelvis. Incorporating these new endoscopic approaches has revolutionized the diagnosis and staging of intraluminal and extraluminal lesions and enabled more accessible and safer tissue acquisition.

Endoscopic ultrasound (EUS)-guided interventions on the liver such as diffuse biopsy and portal pressure gradient measurement are emerging as potential alternatives to percutaneous procedures. The purpose of this editorial was to address all the indications that could potentially make an EUS-guided approach a possible alternative to the percutaneous procedures with respect to the proce-dures that could join the EUS examination such as upper endoscopy for gastro-esophageal varices, pancreaticobiliary investigation with EUS, and other potential advantages in terms of patient safety. The issue of a holistic gastroenterologist approach was also discussed along with the potential for developing clinical research.

Endoscopic ultrasound (EUS) has evolved from a diagnostic to an interventional modality, allowing precise vascular access and therapy. EUS-guided vascular access of the portal vein has received increasing attention in recent years as a diagnostic and therapeutic tool. EUS-guided portal pressure gradient directly measures the hepatic vein portal pressure gradient and is crucial for understanding of liver function and prognostication of liver disease. EUS facilitates the sampling of portal venous blood to obtain circulating tumor cells (CTCs) in pancreatobiliary malignancies. This technique aids in the diagnosis and staging of cancers. EUS-guided interventions have a substantial potential for diagnosing portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma. EUS-guided coil and glue embolization have higher efficacy for the treatment of gastric varices than direct endoscopic glue. Pseudoaneurysm (PsA), a rare vascular complication of acute and chronic pancreatitis, is typically managed with interventional radiology (IR)-guided embolization and surgery. EUS is increasingly used in specialized centers for non-variceal gastrointestinal bleeding, particularly for pseudoaneurysm-related bleeding. There is limited data on EUS-guided intervention for bleeding ectopic varices, rectal varices and Dieulafoy lesions, but it is becoming more widely accepted. In this extensive review, we evaluated both current and potential future applications of EUS-guided vascular interventions, including EUS-guided gastric variceal bleed therapy, rectal and ectopic varices, pseudoaneurysmal bleeding, splenic artery embolization, portal pressure gradient measurement, portal vein sampling for CTCs, fine needle aspiration of PVTT, intrahepatic portosystemic shunt placement, liver tumor ablation and EUS-guided cardiac intervention.

The growing and evolving field of EUS and advanced hepatobiliary endoscopy has amplified traditional upper gastrointestinal endoscopy and unveiled novel options for remaining unsolved hepatobiliary issues, both diagnostically and therapeutically. This conceptually appealing and fascinating integration of endoscopy within the practice of hepatology is referred to as 'endo-hepatology'. Endo-hepatology focuses on the one hand on disorders of the liver parenchyma and liver vasculature and of the hepatobiliary tract on the other hand. Applications hanging under the umbrella of endohepatology involve amongst others EUS-guided liver biopsy, EUS-guided portal pressure measurement, EUS-guided portal venous blood sampling, EUS-guided coil & glue embolization of gastric varices and spontaneous portosystemic shunts as well as ERCP in the challenging context of (decompensated cirrhosis) and intraductal cholangioscopy for primary sclerosing cholangitis. Although endoscopic proficiency however does not necessarily equal in an actual straightforward end-solution for currently persisting (complex) hepatobiliary situations. Therefore, endohepatology continues to generate high-quality data to validate and standardize procedures against currently considered (best available) "golden standards" while continuing to search and trying to provide novel minimally invasive solutions for persisting hepatological stalemate situations. In the current review, we aim to critically appraise the status and potential future directions of endo-hepatology.

Gastrointestinal endoscopy has long been a reliable backbone in the diagnosis and management of hepatobilary disorders and their complications. However, with evolving non-invasive testing, personalised medicine has reframed the utility and necessity of endoscopic screening. Conversely, the growing interest and use of endoscopic ultrasound (EUS) and advanced endoscopy within gastrointestinal units has also opened novel diagnostic and therapeutic avenues for patients with various hepatobiliary diseases. The integration of "advanced endoscopy" within the practice of hepatology is nowadays referred to as "endo-hepatology". In essence, endo-hepatology consists of two pillars: one focusing primarily on disorders of the liver parenchyma, vascular disorders, and portal hypertension, which is mainly captured via EUS, while the other targets the hepatobiliary tract via endoscopic retrograde cholangiopancreatography and advanced imaging. Applications under the umbrella of endo-hepatology include, amongst others, EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, coil and glue embolisation of gastric varices as well as cholangioscopy. As such endo-hepatology could become an attractive concept wherein advanced endoscopy might reinforce the medical management of patients with hepatobiliary disorders and their complications after initial basic work-up. In this review, we discuss current trends and future developments within endo-hepatology and the remaining hurdles to overcome.

Inflammation plays an essential role in the development liver fibrosis.The Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is a central cytoplasmic DNA sensor which can recognize cytoplasmic DNA, known to trigger stimulator of interferon genes (STING) and downstream proinflammatory factors. Here, we investigated the role of cGAS-STING signaling pathway in the pathogenesis of liver fibrosis.Differentially expressed genes (DEGs) in human liver tissue were identified using RNA-Seq analysis. As models of liver fibrosis, chronic Carbon tetrachloride (CCl4) exposure were applied in cGAS-knockout mice. LX-2 cells were co-cultured with human liver sinusoidal endothelial cells (LSECs) to explore the underlying mechanisms of hepatic sinusoidal microthrombosis in an inflammatory microenvironment. The endoscopic ultrasound-guided portal vein pressure gradient (EUS-PPG) method was used to analyze the associations between hepatic sinusoidal microthrombosis and PPG in patients with liver fibrosis and portal hypertension (PTH). The RNA-seq analysis results showed that DEGs were enriched in inflammation and endothelial cell activation. The upregulation of the cGAS-STING signaling exacerbated liver fibrosis and intrahepatic inflammation. It also exacerbated LSECs impairment and increased the contribution of hepatic sinusoidal microthrombosis to liver fibrosis in vivo and in vitro. Prothrombotic mediators and proinflammatory factors were associated with PPG in patients with liver fibrosis and portal hypertension. Therefore, activating cGAS-STING signaling pathway promotes liver fibrosis and hepatic sinusoidal microthrombosis, which may lead to increased portal vein pressure.

There is dramatically increased incidence of several liver diseases worldwide; thus, an unmet need to diagnose and stage these pathological entities heralds the wide application of liver biopsy (LB) techniques. The ways of LB are versatile, including percutaneous LB, transjugular LB, and more recently an approach of minimal invasiveness, that is, EUS-guided LB (EUS-LB). In this review article, we come to the conclusion that EUS-LB may serve as a feasible, reliable, and safe alternative to percutaneous LB and transjugular LB in terms of improved diagnostic yield, excellent sampling performance, and controlled adverse events among patients with focal, infiltrative, and parenchymal liver diseases. Furthermore, extensive efforts have been made to optimize and refine several technical pillars within EUS-LB modality such as the selection of needle size/type, priming manner of biopsy needle, and choice of pass/actuation technique, all of which aim at obtaining better specimen quantity and quality. Another advantageous aspect and unique property pertinent to EUS-guided modality indicate that multiple screening, surveillance, and intervention procedures can be combined into one single endoscopic session. Accordingly, some pilot studies have clarified the clinical usefulness by integrating EUS-LB with simultaneous measurement of portal pressure gradient or examination of liver stiffness. However, more studies, in particular, randomized controlled trials or real-world evidence, are practically warranted to elucidate the validity and safety of EUS-LB as a regular/routine part of managing liver diseases.

Over the past decade, the number of endoscopic procedures relevant to patients with liver disease not only increased but also altered and expanded in terms of indications and applications. "Endohepatology" refers to the integration of advanced endoscopy within the practice of hepatology with endoscopic ultrasound as one of the main pillars. Current applications under the umbrella of endohepatology focus on advanced diagnostics and oncological, vascular, and metabolic interventions. These involve, among others, endoscopic ultrasound (EUS)-guided liver biopsy, EUS-guided portal pressure gradient measurement, and EUS-guided coil and glue embolization of gastric varices. In addition to its conceptually attractive technical and innovative characteristics, endohepatology is also an appealing practical option for daily practice because it can be offered as a "one-stop clinic" intervention where comprehensive endoscopic diagnostic and/or therapeutic testing is performed in a single outpatient visit. In this review, we will discuss current trends and future developments within endohepatology and the remaining hurdles to overcome.

The purpose of this AGA Institute Clinical Practice Update is to review the available evidence supporting and examine opportunities for future research in endoscopic ultrasound-guided vascular investigation and therapies.

This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are advanced endoscopists with expertise in endoscopic ultrasound-guided vascular investigation and therapy.

Endoscopy is and remains an indispensable tool in diagnosing and managing liver disease and its complications. Due to the progress in advanced endoscopy, endoscopy has become an alternative route for many surgical, percutaneous, and angiographic interventions, not only as a backup tool when conventional interventions fail but increasingly as a first-line choice. The term endo-hepatology refers to the integration of advanced endoscopy in the practice of hepatology. Endoscopy is key in the diagnosis and management of esophageal and gastric varices, portal hypertensive gastropathy, and gastric antral vascular ectasia. Endoscopic ultrasound (EUS) can be used for the evaluation of the liver parenchyma, liver lesions, and surrounding tissues and vessels, including targeted biopsy and complemented with new software functions. Moreover, EUS can guide portal pressure gradient measurement, and assess and help manage complications of portal hypertension. It is crucial that each present-day hepatologist is aware of the (rapidly increasing) full spectrum of diagnostic and therapeutic tools that exist within this field. In this comprehensive review, we would like to discuss the current endo-hepatology spectrum, as well as future directions for endoscopy in hepatology.

Endoscopic ultrasound (EUS) has expanded its arena from a mere diagnostic modality to an essential therapeutic tool in managing gastrointestinal (GI) diseases. The proximity of the GI tract to the vascular structures in the mediastinum and the abdomen has facilitated the growth of EUS in the field of vascular interventions. EUS provides important clinical and anatomical information related to the vessels' size, appearance and location. Its excellent spatial resolution, use of colour doppler with or without contrast enhancement and ability to provide images "real-time" helps in precision while intervening vascular structures. Additionally, structures such as venous collaterals or varices can be dealt with optimally using EUS. EUS-guided vascular therapy with coil and glue combination has revolutionized the management of portal hypertension. It also helps to avoid radiation exposure in addition to being minimally invasive. These advantages have led EUS to become an upcoming modality to complement traditional interventional radiology in the field of vascular interventions. EUS-guided portal vein (PV) access and therapy is a new kid on the block. EUS-guided portal pressure gradient measurement, injecting chemotherapy in PV and intrahepatic portosystemic shunt has expanded the horizons of endo-hepatology. Lastly, EUS has also forayed into cardiac interventions allowing pericardial fluid aspiration and tumour biopsy with experimental data on access to valvular apparatus. Herein, we provide a comprehensive review of the expanding paradigm of EUS-guided vascular interventions in GI bleeding, portal vein access and its related therapeutic interventions, cardiac access, and therapy. A synopsis of all the technical details involving each procedure and the available data has been tabulated, and the future trends in this area have been highlighted.

The role of endoscopic ultrasound in the diagnosis and management of chronic liver disease is rapidly increasing. It forms one of the major backbones of endo-hepatology and brings us a step closer to personalized medicine. This review will focus on the particular use of EUS in the diagnosis and management of cirrhotic portal hypertension and potential complications hereof, such as ascites and gastrooesophageal varices. More specifically, EUS-guided Porto-systemic Pressure Gradient (EUS-PPG) measurement, EUS-guided coil and glue embolization of gastric varices, EUS-guided paracentesis and EUS-guided intrahepatic portosystemic shunt creation (IPSS) will be discussed in-depth with regard to clinical status, available data and technical considerations.