Liver international : official journal of the International Association for the Study of the Liver · 2026
Identification of Prognostic Factors and Regulatory Pathways in Porto-Sinusoidal Vascular Disorder.
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Heo Subin, Yoon Do Kyung, Shin Soyeon, Youn Dami, Yoo Youngeun, Song In Hye, Kang Hyo Jeong, Yoon Young-In, Kim Kyunggon, Lee Seung Soo, Chung Sung Won, Choi Jonggi, Lee Danbi, Shim Ju Hyun, Kim Kang Mo, Lim Young-Suk, Lee Han Chu, Muthiah Mark, Lee Ho-Su, Choi Won-Mook
Аннотация
BACKGROUND AND AIMS: Porto-sinusoidal vascular disorder (PSVD) is a rare liver condition characterized by specific histological features primarily affecting the hepatic sinusoidal and periportal vasculature, in the absence of cirrhosis. This study aimed to identify prognostic factors and regulatory pathways associated with PSVD by integrating transcriptomic and clinical data.
METHODS: A total of 114 PSVD patients were included, with 74 followed longitudinally for liver-related events. RNA sequencing was performed on 21 liver samples and compared to six histologically normal livers. Associations between clinical parameters, such as liver-to-spleen volume ratio (LSVR) and fibrosis stage, with liver-related events were assessed. Transcriptomic analyses, including co-expression and cell deconvolution, were conducted based on these parameters.
RESULTS: Among the 114 patients, 32 (28.1%) underwent liver transplantation at diagnosis. LSVR strongly correlated with fibrosis stage, which was significantly associated with liver transplantation (per 1-stage increase: adjusted OR, 14.88; 95% CI: 3.72-59.58). Over a mean follow-up of 6.7 years in the longitudinal cohort, 12 patients (16.2%) experienced liver-related events. LSVR was identified as a significant prognostic marker, with an optimal cut-off value of 1.33 for predicting liver-related events. Transcriptomic analysis based on LSVR and fibrosis stage revealed distinct gene expression patterns and cellular changes in PSVD, including shifts in liver sinusoidal endothelial cell (LSEC) distribution, an increased hepatic stellate cell population, and upregulation of IL-6 signalling, without changes in immune cell composition as the disease progresses.
CONCLUSIONS: This study identified LSVR as a novel prognostic marker in PSVD and suggests that IL-6 trans-signalling-induced endotheliopathy in LSECs may play a role in the proinflammatory and fibrotic changes associated with disease progression.
METHODS: A total of 114 PSVD patients were included, with 74 followed longitudinally for liver-related events. RNA sequencing was performed on 21 liver samples and compared to six histologically normal livers. Associations between clinical parameters, such as liver-to-spleen volume ratio (LSVR) and fibrosis stage, with liver-related events were assessed. Transcriptomic analyses, including co-expression and cell deconvolution, were conducted based on these parameters.
RESULTS: Among the 114 patients, 32 (28.1%) underwent liver transplantation at diagnosis. LSVR strongly correlated with fibrosis stage, which was significantly associated with liver transplantation (per 1-stage increase: adjusted OR, 14.88; 95% CI: 3.72-59.58). Over a mean follow-up of 6.7 years in the longitudinal cohort, 12 patients (16.2%) experienced liver-related events. LSVR was identified as a significant prognostic marker, with an optimal cut-off value of 1.33 for predicting liver-related events. Transcriptomic analysis based on LSVR and fibrosis stage revealed distinct gene expression patterns and cellular changes in PSVD, including shifts in liver sinusoidal endothelial cell (LSEC) distribution, an increased hepatic stellate cell population, and upregulation of IL-6 signalling, without changes in immune cell composition as the disease progresses.
CONCLUSIONS: This study identified LSVR as a novel prognostic marker in PSVD and suggests that IL-6 trans-signalling-induced endotheliopathy in LSECs may play a role in the proinflammatory and fibrotic changes associated with disease progression.