Lipidic obstruction of sinusoids ( LOS ): a potentially serious complication of steatotic liver disease

INTRODUCTION: During routine examination of specimens from patients with steatotic liver disease (SLD), we repeatedly observed a peculiar phenomenon characterized by obstruction of the hepatic sinusoids by lipid vacuoles (lipidic obstruction of sinusoids, LOS). These changes were reminiscent of pseudopeliotic steatosis (PPS), a complication following liver transplantation (LT), but notably occurred outside this context. The aim of our study was to identify diagnostic indicators for LOS and to determine its clinical significance. METHODS: Liver specimens routinely sent to our institute between 2019 and 2024 with SLD were examined for LOS. The extracellular nature of the fat and the compression of the sinusoids were demonstrated by ancillary stains (Gomori, CD68, collagen IV). The extent of the LOS was quantified by measuring the area and maximum diameter of fat lakes. The clinical course of patients with LOS was retrospectively evaluated and correlated with the histological findings. RESULTS: LOS was observed in eight patients, ranging from focal to very extensive extracellular fat. The diagnosis was based on routine histology, supplemented by collagen IV stain highlighting double contours of sinusoids. The morphological findings suggested that lipidic obstruction of the hepatic sinusoids was a key pathophysiological factor. LOS was associated with liver necrosis and activation of macrophages. Patients with LOS exhibited a variable clinical course, ranging from subclinical to severe, including LT or even death. The extent of fat lakes correlated with the severity of the clinical course. CONCLUSIONS: We suggest the term LOS for a particular pattern of liver damage that can occur in SLD outside the transplantation setting and may lead to impaired hepatic blood flow. LOS is associated with a variable clinical presentation, ranging from subclinical to fatal. Clinicians and pathologists should be aware of this complication of SLD, which is diagnosed by liver histology.