Endohepatology expands clinical reach

Endoscopic ultrasound (EUS)–based interventions are approaching noninferiority to established standards in liver biopsy and may reduce rebleeding in gastric varices, but require further validation, standardization, and cost analyses before widespread adoption, according to a narrative review published in Gastro Hep Advances.

For the review, senior author K. Rajender Reddy, MD, of the Division of Gastroenterology and Hepatology at the University of Pennsylvania, and colleagues synthesized emerging data across EUS-guided liver biopsy (EUS-LB), portal pressure gradient measurement (EUS-PPG), gastric varices therapy, elastography, focal liver lesion management, endobariatrics, and liver transplantation applications. They emphasized that although endohepatology offers a potential “one-stop shop,” evidence remains heterogeneous and largely derived from small or single-center studies.

EUS-guided liver biopsy: Comparable adequacy, less pain

Liver biopsy remains indicated when diagnostic or prognostic information cannot be obtained by safer alternatives. Contemporary percutaneous liver biopsy (PCLB) demonstrates high adequacy (98% in a large hepatitis B cohort) and low complication rates (1.4% overall), while a systematic review reported a 2.4% incidence of major complications including bleeding (0.48%) and mortality (0.01%).

Against this benchmark, EUS-LB has shown comparable performance in recent randomized trials. Two meta-analyses of four randomized studies cited in the review reported similar diagnostic adequacy between EUS-LB and PCLB when measured by specimen length and complete portal tracts (CPTs), with lower postprocedural pain scores for EUS-LB (standard mean difference −0.58).

A separate systematic review demonstrated pooled histologic diagnostic rates of 93.9% across nine studies. A more recent meta-analysis of five studies reported diagnostic accuracy of 98.6% for PCLB and 88.3% for EUS-LB, though this difference was attributed in part to earlier fine-needle aspiration devices.

Dr. Reddy and coauthors note that technique refinements, especially use of 19-gauge fine-needle biopsy needles with suction, have improved yield. In a recent multicenter randomized trial, wet suction achieved 99% diagnostic yield and a median of 16 CPTs, outperforming slow-stylet pull in histologic adequacy without increasing adverse events.

Bilobar sampling represents a key theoretical advantage cited in the review, as up to one-third of patients may exhibit a one-stage fibrosis discrepancy between right and left lobes. However, cost remains a barrier: one comparative study reported mean costs of $3,240 for EUS-LB vs $1,824 for PCLB (P < .001).

EUS-PPG: Direct portal pressure measurement

According to the review, hepatic venous pressure gradient (HVPG) remains the gold standard for portal hypertension assessment. HVPG ≥10 mm Hg defines clinically significant portal hypertension (CSPH); >12 mm Hg predicts variceal bleeding; >16 mm Hg increases mortality risk; and >20 mm Hg independently predicts poor survival. Each 1-mm Hg increase raises mortality risk by 3% in transplant candidates.

EUS-PPG measures pressure directly in the portal vein and can detect pressure changes before the liver (presinusoidal) that HVPG might miss. This is especially important in MASLD and portosinusoidal vascular disease.

Animal data cited in the review demonstrated near-perfect correlation between EUS-PPG and HVPG (r = 0.98–0.99). Subsequent human studies report strong correlations: Pearson r = 0.923 in one prospective comparison (mean EUS-PPG 18.07 ± 4.32 mm Hg vs HVPG 18.82 ± 3.43 mm Hg), and an intraclass correlation coefficient 0.82 in another.

Technical success rates range from 92% to 100%, with low adverse event rates. However, sedation may affect readings. For example, in the ENCOUNTER study, HVPG decreased from 14.2 ± 5.1 mm Hg to 11.9 ± 5.2 mm Hg under propofol anesthesia.

The authors call for larger validation studies and standardization of technique and sedation protocols.

Gastric varices: Lower rebleeding with EUS-guided therapy

Cyanoacrylate injection remains standard therapy for gastric varices, achieving primary hemostasis in 82%–94% of cases, though rebleeding rates vary widely. A meta-analysis of 24 studies reported pooled recurrence of 34%, early rebleeding 16%, and late rebleeding 39%.

EUS-guided approaches using glue, coils, or both appear to improve outcomes. A systematic review of 23 studies found a pooled treatment efficacy of 93.7%, obliteration rate 84.4%, and early and late rebleeding rates of 7.0% and 11.6%, respectively.

In a separate meta-analysis of six studies, EUS-guided therapy reduced recurrent bleeding (odds ratio [OR] 0.22) and reintervention rates (OR, 0.29) compared with endoscopic glue alone, without differences in pulmonary embolism (OR 0.34), technical success, or mortality.

A randomized trial comparing coil alone vs coil plus glue reported higher immediate obliteration (86.7% vs 13.3%) and lower rebleeding (3.3% vs 20%) with combination therapy.

Elastography and focal lesions

Authors of the review characterized EUS shear wave elastography (SWE) as investigational. In a prospective study of 42 patients, area under the curve values for advanced fibrosis were 0.87 (VCTE), 0.80 (left lobe EUS-SWE), and 0.78 (right lobe EUS-SWE). For cirrhosis, AUC values were 0.90, 0.96, and 0.90, respectively.

In focal liver lesions, EUS-guided radiofrequency ablation achieved 100% initial ablation across 25 tumors in 20 patients, though 16% developed local progression and 75% experienced intrahepatic recurrence over 27 months.

Moving beyond the ‘one-stop shop’

Despite promising data, the authors caution that robust noninvasive tests for fibrosis and CSPH limit the likelihood that invasive EUS techniques will supplant established tools.

“Goal-directed utilization… appears to be the most promising,” they conclude, emphasizing that innovation must be “balanced against patient safety and outcomes.”

The authors reported having no relevant disclosures.

GI & Hepatology News invited senior author K. Rajender Reddy, MD, of the Division of Gastroenterology and Hepatology at the University of Pennsylvania, to offer additional perspective on the review.

Why is now the right time for this review?

Dr. Reddy: Endohepatology is an evolving field that uses advanced endoscopic techniques to evaluate the liver and biliary tree. While endoscopic ultrasound (EUS) has been available for many years, endohepatology represents an expansion of its applications.

Importantly, endohepatology is not a single procedure but a broad diagnostic and therapeutic platform. It encompasses multiple procedures that address various aspects of liver and biliary disease, including tissue acquisition (biopsy), diagnostic assessment, hemodynamic evaluation, and, in selected cases, therapeutic interventions.

How might this review influence clinical practice?

Dr. Reddy: I believe this review has the potential to influence clinical practice in meaningful ways. Some may argue that there are already well-established methods for assessing the liver and performing therapeutic interventions. However, in certain clinical scenarios, endohepatology may offer a “one-stop” approach.

For example, following liver transplantation, a graft may show signs of dysfunction. In that setting, multiple evaluations are required. We assess the hepatic vasculature to ensure vessel patency, evaluate the liver parenchyma to rule out rejection (often requiring biopsy), and examine the biliary system to exclude strictures or other complications.

Currently, these assessments are often performed in stages — on different days and through separate procedures. As the field advances, endohepatology may allow for a more streamlined, consolidated approach, potentially improving efficiency and patient care.

What gaps in knowledge remain in this area, and what research should be pursued next?

Dr. Reddy: This field is still evolving, and several important gaps remain. Future research must focus on demonstrating that the information obtained through endohepatology is comparable in accuracy to existing standards, while also being less invasive, cost-effective, and efficient.

For example, measurements such as portal pressure gradients are already well established using the transjugular approach. Demonstrating that endoscopic approaches provide equivalent or superior data may be challenging, particularly given the entrenched role of current techniques. Large, well-designed comparative studies will be necessary to establish non-inferiority or superiority.

That said, there are areas where endohepatology may offer clear advantages. One example is the management of gastric varices. Emerging studies suggest that endoscopic ultrasound–guided therapies may offer therapeutic benefits over traditional modalities, although this advantage may not yet be widely appreciated.

The challenge lies in generating sufficiently robust evidence — particularly large-scale studies — to demonstrate superiority over established approaches. However, the potential strength of endohepatology lies in its ability to serve as a “one-stop” platform in selected clinical scenarios, combining diagnostic evaluation and therapeutic intervention in a single setting.

Moving forward, research should focus on comparative effectiveness, cost analysis, patient-centered outcomes, and clearly defining the clinical scenarios in which this integrated approach provides the greatest benefit.