Nobuyuki Toshikuni
I read with great interest the article by Niazi et al. [1] suggesting that liver biopsy for suspected autoimmune hepatitis (AIH) may be safely deferred in non-cirrhotic, antinuclear antibody (ANA)-positive individuals with alanine aminotransferase (ALT) < 101 U/L. While conceptually appealing, the clinical establishment of this ‘non-cirrhotic’ baseline warrants critical reassessment. The authors' deferral strategy hinges entirely on accurately identifying patients as non-cirrhotic prior to withholding histology. In retrospective cohorts, confirming this baseline via routine assessments is methodologically precarious. Systematic reviews explicitly demonstrate that routine laboratory indices exhibit suboptimal diagnostic accuracy for detecting advanced fibrosis and cirrhosis in AIH [2]. Furthermore, conventional cross-sectional imaging inherently depends on gross morphological changes, lacking the sensitivity to consistently detect fully compensated cirrhosis [3]. As Niazi et al. [1] appropriately acknowledge, established AIH-related cirrhosis frequently presents with normal or modest ALT levels despite significant histological activity [4]. Because advanced AIH often progresses without overt clinical signs, subjective clinical evaluation risks missing insidious disease [4]. The inherent risk within this specific population is further underscored by the authors' own finding: a striking 26.9% (21/78) of their cohort with mild ALT elevation and positive ANA harboured biopsy-proven cirrhosis [1]. Importantly, 9.5% (2/21) of these cirrhotic cases were confirmed as AIH-related cirrhosis requiring long-term immunosuppressive therapy. This non-negligible prevalence confirms that this specific biochemical phenotype frequently coexists with advanced liver disease. Consequently, actively selecting patients with highly suspected advanced liver fibrosis serves as an effective strategy for diagnosing silent AIH-related cirrhosis, directly challenging the assertion that routine biopsy yields limited diagnostic value for AIH in this subgroup. Given the inadequacy of routine assessments, any clinical strategy advocating biopsy deferral must systematically incorporate dedicated, objective fibrosis staging to identify this high-risk subset. I propose the standardized application of widely accessible, ultrasound-based elastography as the optimal modality to bridge this diagnostic gap. Notably, the authors' focus on patients with mild aminotransferase elevations presents an ideal physiological scenario for its use because severe hepatic necroinflammation—which artificially elevates stiffness readings—is minimized in this cohort; elastography operates with high precision for accurately detecting true advanced fibrosis [2, 5, 6]. Therefore, rather than broadly deferring biopsy based on aminotransferases and routine clinical evaluations alone, objective ultrasound-based elastography must serve as a mandatory prerequisite. If elastography confirms the absence of advanced fibrosis, deferral is structurally safe. Conversely, if elastography is unavailable or indicates elevated stiffness, liver biopsy remains essential—not merely to evaluate alternative aetiologies as the authors suggest, but to accurately stage fibrosis and avoid missing silent AIH-related cirrhosis. Without this objective prerequisite, deferring histology risks leaving clinically severe liver disease untreated. Nobuyuki Toshikuni: conceptualization, writing – original draft, writing – review and editing. The author has nothing to report. The author declares no conflicts of interest. This article is linked to Niazi et al. paper. To view this article, visit https://doi.org/10.1111/apt.70665. The author has nothing to report.