SGLT-2 inhibitors in portal hypertension-related ascites: A case series and potential insights into pathophysiology

Background Researches about the pathophysiology of the ascites in cirrhosis continues to evolve. The underfilling hypothesis is the best-known explanation of ascites formation, but the possible contribution of overfilling has become more attention. Aim To discuss, in light of the literature, whether the different responses to an SGLT2 inhibitor in patients with ascites of different etiologies may reflect differences in the pathophysiological processes underlying ascites formation. Case series We present four patients with ascites. Two had grade 3 ascites secondary to noncirrhotic portal vein thrombosis (NCPVT) of different etiologies; the other two had Child-Pugh class B cirrhosis and grade 3 ascites. Each had been receiving furosemide and spironolactone, and dapagliflozin 10 mg was introduced for the management of ascites. In the two patients with NCPVT, ascites regressed after dapagliflozin until it was no longer detectable on physical examination. No clinically detectable ascites recurred during the one-year follow-up. In the patients with cirrhosis, ascites also decreased after dapagliflozin but remained detectable on physical examination. The frequency of paracentesis nevertheless declined. Conclusion In ascites associated with NCPVT, perhaps the predominant pathophysiological process may be angiotensin II-mediated proximal tubular reabsorption secondary to underfilling. In cirrhosis, overfilling appears to contribute alongside underfilling.