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Review
. 2023 Mar 14;12(6):2253.
doi: 10.3390/jcm12062253.

The Effects of SGLT2 Inhibitors on Liver Cirrhosis Patients with Refractory Ascites: A Literature Review

Yasunori Miyamoto  1 , Akira Honda  2 , Seiji Yokose  3 , Mariko Nagata  1 , Jiro Miyamoto  1
Affiliations
Review

The Effects of SGLT2 Inhibitors on Liver Cirrhosis Patients with Refractory Ascites: A Literature Review

Yasunori Miyamoto et al. J Clin Med. .

Abstract

Decompensated liver cirrhosis is often complicated by refractory ascites, and intractable ascites are a predictor of poor prognosis in patients with liver cirrhosis. The treatment of ascites in patients with cirrhosis is based on the use of aldosterone blockers and loop diuretics, and occasionally vasopressin receptor antagonists are also used. Recent reports suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors may be a new treatment for refractory ascites with a different mechanism with respect to conventional agents. The main mechanisms of ascites reduction with SGLT2 inhibitors appear to be natriuresis and osmotic diuresis. However, other mechanisms, including improvements in glucose metabolism and nutritional status, hepatoprotection by ketone bodies and adiponectin, amelioration of the sympathetic nervous system, and inhibition of the renin-angiotensin-aldosterone system, may also contribute to the reduction of ascites. This literature review describes previously reported cases in which SGLT2 inhibitors were used to effectively treat ascites caused by liver cirrhosis. The discussion of the mechanisms involved is expected to contribute to establishing SGLT2 therapy for ascites in the future.

Keywords: ascites; decompensated liver cirrhosis; diuretics; sodium–glucose cotransporter 2 (SGLT2) inhibitors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanism of the effects of SGLT2 inhibitors on liver cirrhosis patients with refractory ascites. ANP, atrial natriuretic peptide; AVP, arginine vasopressin.
Figure 2
Figure 2
Point of action and mechanism of each diuretic. Loop diuretics inhibit Na+/K+/2Cl− co-transporters in the ascending limb, thereby inhibiting Na+/K+ absorption. Diuresis is indicated by increased Na+ excretion. Aldosterone binds to aldosterone receptors and subsequently upregulates epithelial sodium channel (ENaC) in the collecting duct, which promotes apical Na+ reabsorption. Aldosterone also activates basolateral Na+/K+-ATPase for Na+ excretion from the cell to the interstitial fluid and K+ absorption from the interstitial fluid to the cell. Inhibition of these reactions by aldosterone antagonists increases urinary Na+ excretion, resulting in diuresis. AVP binds to vasopressin receptor type 2 (V2R) and upregulates the expression and translocation of aquaporin-2 (AQP-2) to the cell membrane on the luminal side of the tubule, resulting in water reabsorption. Vaptans antagonize arginine vasopressin (AVP) and inhibit H2O channel activity. Thus, water diuresis occurs.
Figure 3
Figure 3
Clinical course of our case. This case was a 59-year-old Japanese man (patient 5 in Table 1). Since his renal function became worse after using diuretics, concentrated ascites reinfusion therapy (CART) was selected. After six rounds of CART, administration of empagliflozin was started. Subsequently, the ascites improved markedly. Red arrows indicate CART administration. Clinical data and radiological examinations (A) before CART, (B) just prior to empagliflozin administration, (C) after using empagliflozin for 28 days, and (D) after using empagliflozin for 3 months. This figure was adapted from a previous study [21].
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