Hepatic Sinusoidal Obstruction Syndrome Induced by Pyrrolizidine Alkaloids: Mechanistic Insights, Emerging Biomarkers, and Therapeutic Innovations

Hepatic sinusoidal obstruction syndrome (HSOS) is a microcirculatory disorder of the liver that poses a serious threat to human health. Pyrrolizidine alkaloids (PAs), a class of toxins widely found in plants, are often ingested accidentally and are one of the major causes of HSOS. The pathophysiological mechanism of PA‐HSOS is complex and primarily involves the metabolic activation of PAs to form highly reactive intermediates, which directly damage liver sinusoidal endothelial cells and disrupt the homeostasis of the hepatic sinusoidal microcirculation, thereby triggering toxic effects across multiple pathways, including coagulation‐fibrinolysis imbalance, mitochondrial dysfunction, and disruption of the enterohepatic axis. Clinically, patients typically present with ascites, hepatomegaly, and jaundice. Although most patients exhibit abnormal liver function, there are no specific diagnostic markers. In recent years, various potential biomarkers based on PA metabolism, coagulation system activation, metabolomics, and transcriptomics have been identified, improving the diagnostic specificity of PA‐HSOS. Regarding treatment, in addition to traditional approaches such as symptomatic and supportive care, anticoagulation, transjugular intrahepatic portosystemic shunt, and liver transplantation, recent studies have shown that various natural compounds and antithrombotic drugs can effectively alleviate PA‐induced liver injury. This article systematically reviews the molecular mechanisms, clinical manifestations, diagnostic and therapeutic advances, and translational challenges of PA‐HSOS, offering a reference for a deeper understanding of this disease and the development of intervention strategies.