Endoscopic ultrasound-guided liver biopsy: Are we ready for routine use?

Abstract

Endoscopic ultrasound-guided liver biopsy (EUS-LB) is increasingly used for the evaluation of parenchymal liver disease, with recent multicenter data demonstrating high diagnostic yield and a low rate of serious adverse events. While EUS-LB offers technical flexibility through different needle sizes, suction techniques, and limited passes, its overall diagnostic outcomes, including specimen length, portal tract count, and sample adequacy, are comparable to standard percutaneous liver biopsy. Despite these encouraging results, EUS-LB is more invasive, requiring sedation and endoscopic expertise, and is substantially more costly than percutaneous-liver biopsy. Therefore, while EUS-LB is valuable in select clinical scenarios, current evidence does not support its routine use for parenchymal liver disease, and further prospective studies are needed to define its role relative to established percutaneous approaches.

Key Words: Endoscopic ultrasound-guided liver biopsy; Percutaneous liver biopsy; Endoscopic ultrasound-guided-fine-needle biopsy; Diagnostic yield; Parenchymal liver disease

Core Tip: Endoscopic ultrasound-guided liver biopsy (EUS-LB) has emerged as a feasible and safe alternative to percutaneous liver biopsy for evaluating parenchymal liver disease. However, comparative evidence shows equivalent diagnostic adequacy and safety between the two techniques, with percutaneous liver biopsy yielding lower procedural costs. EUS-LB remains more invasive and resource-intensive, requiring endoscopic expertise and sedation. While EUS-LB is valuable when combined with other endoscopic interventions or when percutaneous access is not feasible, current data do not justify its routine use. Future studies should focus on cost-effectiveness, standardization, and patient-centered outcomes before broader adoption.

INTRODUCTION

Liver biopsy (LB) remains an essential diagnostic tool for the evaluation of parenchymal liver disease, particularly when noninvasive tests are inconclusive or histological confirmation is required. The traditional percutaneous LB (PC-LB) has long been the reference standard, offering excellent diagnostic yield, low complication rates, and broad availability[1]. In recent years endoscopic ultrasound-guided LB (EUS-LB) has emerged as a promising alternative, offering access to both hepatic lobes during the same session and potential integration with other endoscopic interventions such as endoscopic ultrasound-based procedures (e.g., portosystemic pressure measurement) or evaluation of biliary disease[2].

The multicenter retrospective study published by Alali et al[3] confirms the technical feasibility and safety of EUS-LB in patients with suspected parenchymal liver disease. The authors report a high diagnostic yield and a low rate of serious adverse events, with improved tissue quality achieved through the use of 19-gauge fine-needle biopsy needles, the wet-heparin suction technique, and two or fewer needle passes. These results are consistent with earlier single-center experiences and systematic reviews supporting the procedural reliability of EUS-LB[4,5].

COMPARATIVE EFFICACY, COSTS AND LIMITATIONS

When placed in context with comparative evidence, it becomes clear that EUS-LB and PC-LB perform similarly in diagnostic outcomes but differ substantially in invasiveness and cost. A 2023 meta-analysis by Chandan et al[6] including five studies and 748 patients (276 EUS-LB and 472 PC-LB) reported that, although overall diagnostic adequacy and adverse event rates were similar between the two techniques, PC-LB demonstrated slightly higher diagnostic accuracy (98.6% vs 88.3%, odds ratio = 1.65, P = 0.04), with significantly longer specimen length and a greater number of complete portal tracts, confirming its continued advantage in tissue yield despite comparable safety and feasibility profiles[6].

Similarly, Facciorusso et al[7] performed a systematic review and meta-analysis including 899 patients from seven studies and found no significant differences between EUS-LB and PC-LB in total specimen length (29.9 mm vs 29.7 mm), number of portal tracts, or sample adequacy (96.4% vs 99%), respectively (P = 0.11). Severe adverse events were rare and comparable in both groups. These findings confirm that EUS-LB achieves diagnostic yields equivalent to PC-LB, but without clear superiority in histologic quality or safety[7].

Since only a meta-analysis restricted to randomized controlled trials can provide the highest-quality evidence when comparing two interventional techniques, a recent meta-analysis based exclusively on four randomized controlled trials further confirmed that EUS-LB and PC-LB achieve comparable sample adequacy [risk ratio = 1.18; 95% confidence interval (CI): 0.58-2.38; P = 0.65] and diagnostic accuracy (risk ratio = 1.00; 95%CI: 0.95-1.05; P = 0.88), although percutaneous biopsy yielded significantly longer maximum specimen cores (mean difference -3.11 mm; 95%CI: -5.51 to -0.71; P = 0.01)[8].

While safety and performance equivalence are encouraging, economic and practical considerations remain central to determining whether EUS-LB should be adopted for routine use. EUS-LB is inherently more invasive, as it requires conscious or deep sedation, specialized equipment, and an experienced endosonographer[2]. In contrast, PC-LB can be performed quickly under ultrasound guidance with minimal infrastructure, often on an outpatient basis[1]. Cost comparisons demonstrate that EUS-LB is substantially more expensive: Bang et al[9] reported procedural costs of approximately United States dollar 3240 for EUS-LB compared with United States dollar 1824 for PC-LB, nearly a twofold difference without significant improvement in diagnostic accuracy or safety.

Furthermore, EUS-guided biopsy remains operator-dependent and extreme variability exists regarding needle selection, needle gauge, needle tip design, and suction technique, and these factors significantly influence specimen adequacy and diagnostic yield, contributing to substantial heterogeneity among published studies[10-12]. Evidence from comparative studies indicates that 19G fine-needle biopsy needles, particularly those with a Franseen tip, consistently provide longer core specimens, higher numbers of complete portal tracts, and superior histologic adequacy compared with smaller-gauge needles, Tru-Cut needles, or standard fine-needle aspiration needles[2,4]. About technique, tissue acquisition appears to be further optimized by the use of wet suction (especially heparin-primed) or slow-pull methods, both of which have demonstrated improved specimen integrity and portal tract yield compared with dry suction[2,4]. PC-LB, on the other hand, has decades of optimization, well-defined quality metrics, and broad reproducibility across centers[1].

PATIENT-CENTERED OUTCOMES

Comparative data showed that EUS-LB may be associated with shorter recovery and monitoring times compared with other biopsy modalities. Prior studies have demonstrated significantly reduced post-procedural observation time for EUS-LB compared with PC-LB (3 hours vs 4.2 hours, P = 0.004), as well as shorter recovery times when compared with transjugular LB (90 minutes vs 141.3 minutes, P = 0.004)[13,14]. Moreover pain, a frequent minor complication of LB, appears to be both less common and less severe following EUS-LB, with patients reporting significantly lower pain scores compared with percutaneous biopsy and a decreased incidence of post-procedural discomfort relative to transjugular biopsy[15].

EUS-LB AND CONCOMITANT OTHER PROCEDURES

One area where EUS-LB may provide distinct clinical value is in combination with other endoscopic procedures, particularly in complex or multidisciplinary settings. For example, in liver transplant recipients, post-transplant abnormalities in liver function often necessitate multiple diagnostic modalities, including imaging, biopsy, and endoscopic retrograde cholangiopancreatography. The ability to perform EUS-LB concurrently with other endoscopic procedures in the same session represents a promising strategy to streamline patient management, reducing procedural burden, overall costs, and resource utilization[2]. In this setting, a recent case series evaluated 12 consecutive liver transplant recipients undergoing single-session EUS-LB and endoscopic retrograde cholangiopancreatography for abnormal liver function tests[16]. Tissue adequacy was achieved in 100% of cases, with anastomotic stricture (75%) and T-cell-mediated rejection (66.7%) being the most frequent diagnoses. No. 30-day adverse events were observed, supporting the feasibility and safety of this integrated approach[13]. Similarly, Hajifathalian et al[17] demonstrated the technical feasibility of simultaneous EUS-LB and EUS-guided portosystemic pressure measurement, with 100% success in gradient assessment and 96% success in EUS-LB. These results underscore the growing potential of EUS as a multifunctional diagnostic and therapeutic platform.

CONCLUSION

Taken together, the available evidence suggests that EUS-LB is a safe and effective alternative to PC-LB, but not yet a replacement. Its use should be reserved for selected scenarios, such as when percutaneous access is contraindicated (e.g., severe obesity or ascites) or when endoscopic ultrasound or endoscopy is already indicated for other diagnostic purposes (e.g., biliary obstruction, portal pressure gradient measurement). Routine use of EUS-LB for isolated parenchymal liver disease, however, is not justified given its higher cost, procedural complexity, and the absence of clear diagnostic or safety superiority. Indeed, it must be considered that in the present era of cost containment, financial analysis is critical in healthcare decision-making, particularly for commonly indicated procedures such as LB. The recent multicenter study by Alali et al[3] adds valuable evidence supporting the feasibility and safety of EUS-LB; however, broader implementation in routine practice should await further prospective trials evaluating cost-effectiveness, patient-centered outcomes, and long-term safety. Current hepatology and gastroenterology society guidelines continue to endorse percutaneous as the standard approach for histologic evaluation of parenchymal liver disease[1]. However, EUS-guided LB is beginning to be recognized as a feasible method that can be considered as an alternative to standard techniques[1]. For now, EUS-LB should be regarded as a complementary, rather than competing, modality to percutaneous biopsy, representing a sophisticated tool best reserved for specific, well-defined clinical contexts rather than standard use in all patients with liver disease.

ACKNOWLEDGEMENT

We are writing this paper on behalf of the I-EUS group.