Letter to the Editor: Endoscopic ultrasound-guided liver biopsy for parenchymal disease: Feasibility, safety, and future considerations

Abstract

This invited commentary discusses the recent study by Alali et al, published in the World Journal of Gastrointestinal Endoscopy, which investigated the feasibility and safety of endoscopic ultrasound-guided liver biopsy (EUS-LB) for diagnosing parenchymal liver disease. The study demonstrated a high diagnostic yield and a low rate of serious complications, supporting the efficacy of EUS-LB as an alternative to percutaneous liver biopsy. The study also highlighted technical factors that improve tissue acquisition. While commending the multi-center findings and technical insights, we discuss limitations of the retrospective design and modest sample, compare EUS-LB with traditional biopsy modalities, and emphasize the need for larger prospective studies to validate and generalize these results.

Key Words: Endoscopic ultrasound; Liver biopsy; Parenchymal liver disease; Fine needle aspiration; Fine needle biopsy

Core Tip: Endoscopic ultrasound-guided liver biopsy is an established alternative to percutaneous biopsy for parenchymal liver disease. Alali et al report high diagnostic adequacy and a low rate of serious adverse events, reinforcing existing evidence of safety and effectiveness. Their findings suggest that the use of a 19-gauge core biopsy needle and wet heparin suction improves specimen quality. However, the retrospective design and limited sample size warrant cautious interpretation, and larger prospective studies are needed to confirm these observations and refine optimal biopsy techniques.

TO THE EDITOR

We read with great interest the multicenter retrospective cohort study by Alali et al[1], published in the World Journal of Gastrointestinal Endoscopy, on the feasibility and safety of endoscopic ultrasound-guided liver biopsy (EUS-LB) for diagnosing parenchymal liver disease. This favorable safety profile aligns with prior studies and meta-analyses suggesting that EUS-LB is as safe and effective as percutaneous liver biopsy (PLB), with a comparably high diagnostic yield and a low complication rate[2]. Despite the high overall diagnostic adequacy, only 54% of specimens fulfilled the European Association for the Study of the Liver quality criteria, and 34% met the more stringent American Association for the Study of Liver Diseases standards. Use of a 19-gauge core biopsy needle was associated with a marked improvement in these quality metrics; however, this advantage did not result in a significant difference in diagnostic adequacy between fine needle biopsy and fine needle aspiration in the present study. The use of wet heparinized suction was associated with improved specimen quality. These technical insights provided by Alali et al[1] are valuable for informing emerging best practices to obtain optimal histological specimens via EUS-LB[3].

Multiple randomized controlled trials and subsequent meta-analyses have already demonstrated that EUS-LB achieves diagnostic adequacy comparable to PLB, with similar or lower rates of complications and improved patient tolerance attributable to procedural sedation[4]. Recent systematic reviews and meta-analyses have further confirmed these conclusions, positioning EUS-LB as an established alternative rather than an investigational technique[2,5]. Within this context, the primary contribution of the present study lies in its exploration of technical factors, specifically needle type, suction technique, and number of passes, that influence histological specimen quality.

FURTHER DISCUSSION

Nevertheless, several aspects of this study merit further discussion. First, the retrospective design inevitably introduces limitations related to selection bias and dependence on the accuracy and completeness of medical records. In the present study, it remains unclear under what specific circumstances EUS-LB was selected over conventional PLB or transjugular liver biopsy (TJLB). Patient-related factors such as obesity, coagulation status, or the presence of concurrent indications for endoscopy may have influenced procedural choice, yet these details are not fully delineated. Without randomized allocation or prospective standardization, unmeasured confounders may have affected both procedural outcomes and complication rates. Prospective studies with predefined inclusion criteria and standardized indications would strengthen the validity of conclusions regarding feasibility and safety.

Second, although the sample size of fifty patients is comparable to some previously published single-center series, it remains relatively modest. With only seven cases of diagnostic inadequacy and a single major bleeding event, the statistical power to detect meaningful predictors of these outcomes was limited. The authors performed multivariate logistic regression to identify factors associated with diagnostic adequacy, yet no variable reached statistical significance. This finding is not unexpected given the low event rate and limited cohort size, as detecting subtle differences would require a substantially larger population. While the data suggest a numerical trend toward higher adequacy with fine-needle biopsy compared with fine-needle aspiration, the study is underpowered to demonstrate equivalence or small effect sizes at conventional significance thresholds. Similarly, the occurrence of only one bleeding complication precludes meaningful comparison of bleeding risk across needle types or suction techniques. Expanding the sample size in future investigations will be essential not only to better estimate the true incidence of adverse events but also to enable more granular and reliable subgroup analyses.

Third, the generalizability of the findings may be constrained by the specific population and clinical setting. All patients were recruited from two tertiary care centers within a single country, and the demographic profile may differ from that of liver biopsy populations in other regions. In many healthcare systems, liver biopsies are more frequently performed in older individuals with advanced metabolic or viral liver disease, or in populations with different comorbidity burdens[6]. It is reassuring that the diagnostic performance reported in this study is broadly consistent with historical data from PLB, suggesting that the central findings are robust. However, clinical practice patterns vary considerably across institutions and regions. In some centers, PLB remains the default approach because of its simplicity and widespread availability, with EUS-LB reserved for patients in whom percutaneous access is challenging. In other settings, EUS-LB is increasingly adopted because of its ability to obtain tissue under direct visualization and to combine biopsy with diagnostic endoscopy in a single session[7]. The present study does not explicitly clarify whether any patients were considered unsuitable for PLB. Clearer reporting of inclusion and exclusion criteria and the rationale for selecting EUS-LB would help readers better understand the clinical context and determine how these findings may apply to their own patient populations.

Fourth, consideration of how EUS-LB compares with other biopsy modalities in terms of practical advantages and limitations is important. One established benefit of EUS-LB is improved patient comfort, as procedural sedation is associated with lower pain perception compared with PLB performed under local anesthesia[8]. The low rate of serious adverse events observed in this study reinforces prior evidence that EUS-LB has a safety profile comparable to that of PLB when performed in appropriately selected patients. Additional advantages include the ability to sample either hepatic lobe when necessary and to integrate tissue acquisition with gastrointestinal endoscopic evaluation. These features may be particularly useful in patients who require endoscopy for portal hypertension assessment or other gastrointestinal indications. Conversely, EUS-LB requires specialized equipment and operator expertise that may not be universally available. Procedural costs, endoscopy suite utilization, and anesthesia support may further limit its adoption in resource-constrained settings. Moreover, TJLB remains indispensable for patients at high risk of bleeding, as it allows tissue acquisition via the vascular route with intrinsic hemostatic control. EUS-LB, similar to PLB, still carries bleeding risk if coagulation abnormalities are not adequately corrected. Consequently, rather than replacing traditional techniques, EUS-LB is more likely to serve as a complementary modality tailored to individual patient characteristics and institutional resources. Comparative studies and cost-effectiveness analyses would be valuable in clarifying the scenarios in which this approach offers the greatest overall benefit.

CONCLUSION

In conclusion, Alali and colleagues have provided a careful multicenter evaluation of EUS-LB and contributed additional real-world evidence supporting its feasibility and safety in patients with medical liver disease. The study is particularly valuable for its focus on technical parameters that influence specimen quality, offering practical guidance for optimizing tissue acquisition. At the same time, the inherent limitations of a small retrospective cohort necessitate cautious interpretation of the findings. Larger prospective studies involving more diverse patient populations are needed to validate these observations, better define complication risks, and refine best practice recommendations. Direct comparisons with PLB and TJLB across different clinical contexts will further clarify the optimal role of EUS-LB.