Chen TT, Gou HX, Luo ZL. Evaluation of hepatic sonic hedgehog protein expression in the diagnosis of metabolic dysfunction-associated steatohepatitis. World J Hepatol 2026; 18(6): 120134 [DOI: 10.4254/wjh.120134]
Corresponding Author of This Article
Zhu-Lin Luo, PhD, Professor, Department of College of Medicine, Southwest Jiaotong University, No. 111 North Section 1, Second Ring Road, Chengdu 610083, Sichuan Province, China. lzl810130@163.com
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Gastroenterology & Hepatology
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review-article
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Chen TT, Gou HX, Luo ZL. Evaluation of hepatic sonic hedgehog protein expression in the diagnosis of metabolic dysfunction-associated steatohepatitis. World J Hepatol 2026; 18(6): 120134 [DOI: 10.4254/wjh.120134]
World J Hepatol. Jun 27, 2026; 18(6): 120134 Published online Jun 27, 2026. doi: 10.4254/wjh.120134
Evaluation of hepatic sonic hedgehog protein expression in the diagnosis of metabolic dysfunction-associated steatohepatitis
Zhu-Lin Luo, Hao-Xian Gou, Tian-Tian Chen
Tian-Tian Chen, Zhu-Lin Luo, Department of College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
Tian-Tian Chen, Hao-Xian Gou, Zhu-Lin Luo, Department of General Surgery, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
Co-corresponding authors: Hao-Xian Gou and Zhu-Lin Luo.
Author contributions: Chen TT and Gou HX wrote the original draft; Luo ZL contributed to conceptualization, writing, reviewing and editing; Chen TT and Luo ZL participated in drafting the manuscript; Gou HX and Luo ZL contributed equally to this manuscript as co-corresponding authors. All authors have read and approved the final version of the manuscript.
AI contribution statement: During the preparation of this manuscript and answering reviewers document, the authors used ChatGPT only to translate portions of the text, correct grammar, and polish the language. The AI tool was not used to generate any academic content, nor was it involved in the study design, data analysis, interpretation of results, formulation of conclusions, or figure generation. After using the AI tool, the authors carefully reviewed, revised, and verified the relevant content. The authors take full responsibility for the academic content and views expressed in the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Zhu-Lin Luo, PhD, Professor, Department of College of Medicine, Southwest Jiaotong University, No. 111 North Section 1, Second Ring Road, Chengdu 610083, Sichuan Province, China. lzl810130@163.com
Received: February 26, 2026 Revised: April 12, 2026 Accepted: May 13, 2026 Published online: June 27, 2026 Processing time: 125 Days and 0.6 Hours
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of metabolic dysfunction-associated fatty liver disease, with diagnosis relying on liver biopsy. The identification of ballooned hepatocytes in routine hematoxylin-eosin staining is subjective and exhibits significant interobserver variability. Sonic hedgehog homolog (SHH) is specifically expressed in ballooned hepatocytes and holds potential as a positive immunohistochemical marker. This review evaluates the diagnostic value of SHH expression in MASH based on available evidence. Studies demonstrate that SHH staining improves the consistency of interpretation of ballooned hepatocytes and correlates with disease severity, serum biomarkers, and fibrosis staging. However, most evidence comes from single-center retrospective studies with a limited number of observers. The independent predictive value of SHH requires validation through prospective multicenter cohort studies. In summary, SHH immunohistochemistry is a promising adjunctive diagnostic tool for MASH, though its clinical application remains in the preliminary stages.
Core Tip: Sonic hedgehog homolog (SHH) is specifically expressed in ballooned hepatocytes and can be detected by immunohistochemistry. SHH staining may improve the consistency of ballooned hepatocyte interpretation and is associated with the severity of metabolic dysfunction-associated steatohepatitis. However, current evidence primarily comes from single-center retrospective studies. SHH immunohistochemistry is a promising adjunctive diagnostic tool, but multicenter prospective validation is still required before routine clinical application.
