Editorial: The Role of Liver Biopsy in <scp>ANA</scp> Positive Subjects. Authors' Reply

We thank Dr. Björnsson for his thoughtful editorial [1] on our recent manuscript, ‘Diagnostic Impact of Liver Biopsy Among Antinuclear Antibody (ANA)–Positive Individuals With Mild Liver Enzyme Elevation’ [2]. We agree that, at both the higher (ALAT> 1000 U/L) and lower (ALAT< 101 U/L) extremes of liver enzyme abnormalities, liver biopsy may not be required to establish or exclude a diagnosis of autoimmune hepatitis (AIH), similar to what has been suggested before by Björnsson and Hirschfield [3]. In this context, current guidelines mandating biopsy as a diagnostic pre-requisite may be overly prescriptive [4]. A substantial diagnostic ‘gray zone’, however, exists among patients with moderately elevated liver enzymes, in whom histological assessment increases diagnostic certainty and remains crucially important. This consideration is particularly relevant given the well-recognized long-term risks of immunosuppressive therapy, including malignancy, opportunistic infection and renal dysfunction [5]. In comparison, the procedural risk of liver biopsy is low. In our cohort, only 1/313 (0.32%) patients experienced major complications, consistent with large international series demonstrating very low procedure-related mortality [6]. An additional aspect, not addressed in our study, is the psychological impact of liver biopsy on both patients and clinicians. Patients are frequently referred with an expectation of biopsy, and deferring the procedure may contribute to ongoing uncertainty and psychological burden. Similarly, clinicians may favour biopsy to mitigate even a small residual diagnostic risk [7]. Moreover, liver biopsy may occasionally reveal alternative unsuspected diagnoses with potential implications for management. In summary, the decision to perform a liver biopsy in suspected AIH is multifaceted. The current European guideline recommendation to universally require biopsy for diagnosis appears overly stringent, particularly given the lack of robust supporting evidence, as there are no studies demonstrating that routine biopsy prior to treatment improves clinical outcomes [3]. Although our retrospective study has inherent limitations, it provides a data-driven foundation for omitting liver biopsy in patients with mild enzyme elevations and without cirrhosis, enabling informed discussions with patients regarding the rationale behind this approach. The authors' declarations of personal and financial interests are unchanged from those in the original article [2]. David Mehdi Asgher Niazi: writing – original draft, methodology, data curation, investigation, formal analysis, visualization. Conrad Rauber: writing – review and editing, writing – original draft, conceptualization, methodology, supervision, project administration, resources, investigation, validation, data curation. The authors have nothing to report. This article is linked to Niazi et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70665 and https://doi.org/10.1111/apt.70698. The data that support the findings of this study are available from the corresponding author upon reasonable request.