Understanding clinically significant portal hypertension: an in-depth look at pathogenesis, diagnosis and treatment

The development of clinically significant portal hypertension (CSPH) represents one of the strongest predictive biomarkers for disease progression in patients with compensated advanced chronic liver disease (cACLD). Chronic liver injury triggers both intra- and extrahepatic mechanisms, giving rise to an increasing portal pressure and a self-perpetuating cycle with worsening risks of liver-related complications and mortality. Diagnosing CSPH becomes challenging in patients with advanced but compensated chronic liver disease where CSPH is not apparent clinically. Approximately 60% of patients with cACLD will have CSPH, representing a critical window for intervention to reduce portal pressure and prevent complications. The current gold standard for portal pressure measurement, the hepatic venous pressure gradient, is impractical for widespread use. Emerging diagnostic tools aim to address this limitation. Techniques such as endoscopic ultrasound-guided portal pressure gradient measurement, and noninvasive approaches using imaging methods, elastography (targeting liver and/or spleen) and serum markers, offer alternatives for CSPH detection, and moreover, can guide treatment decisions. Non-selective beta-blockers are known to reduce morbidity and mortality in patients with CSPH. Unfortunately, they remain the only approved therapy for CSPH and they are not effective in reducing portal pressure in all patients, highlighting the urgent need for additional therapeutic options as well as practical methods to evaluate treatment response. Recent innovations and ongoing research are steering the field toward a more personalized approach, where diagnosis, treatment and follow up are tailored to individual patient risk profiles. This evolution holds the potential to improve outcomes in patients with CSPH.