Weaning from concentrated ascites reinfusion therapy for refractory ascites by SGLT2 inhibitor.

Ascites associated with decompensated liver cirrhosis is often difficult to control with diuretics [1]. Cell-free and concentrated ascites reinfusion therapy (CART) is one palliative treatment for such patients, but complete withdrawal from CART is challenging [2]. We treated a case of refractory ascites due to liver cirrhosis for which frequent CART was required to ease abdominal distension and dyspnea. After administration of the sodium-glucose cotransporter 2 (SGLT2) inhibitor, the ascites was markedly reduced and we could discontinue CART. Only a limited number of cases for the treatment of ascites with SGLT2 inhibitors have been reported and the effects of SGLT2 inhibitors on patients treated with CART have not been reported previously.

The patient was a 59-year-old Japanese man with decompensated alcoholic cirrhosis and type 2 diabetes (Figure 1). To control the ascites, we administered diuretics (20 mg/day furosemide and 25 mg/day spironolactone) and placed the patient on a salt-restricted diet. However, when furosemide was increased to 40 mg/day, his renal function became worse. We selected CART to relieve his abdominal distension and dyspnea due to the exacerbation of the ascites. After six rounds of CART we began administration of 10 mg/day empagliflozin (SGLT2 inhibitor) because of increased blood glucose levels. Surprisingly, the treatment with empagliflozin markedly improved his abdominal distension, reducing his abdominal circumference. We were then able to discontinue CART and reduce his diuretics. His ascites was well controlled for at least 6 months after stopping CART, with minimal diuretics and empagliflozin. The patient had an additional ∼800 mmol sodium in the body (plasma sodium was 133 mmol/L) and ∼6 kg of extracellular fluid loss was observed by adding empagliflozin. Thus the triple tubular blockade (proximal tubule, loop of Henle and distal tubule) by empagliflozin, furosemide and spironolactone prevented this sodium from accumulating again.

FIGURE 1:

Clinical course of the present case. Red arrows indicate cell-free and 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.

Only three cases of SGLT2-inhibitor treatment of refractory ascites have been reported (Table 1). Two cases were cirrhosis due to nonalcoholic steatohepatitis (NASH) [3] with comorbid type 2 diabetes. They were treated with empagliflozin or canagliflozin. The other case was cirrhosis due to primary biliary cholangitis (PBC) with type 2 diabetes and was treated with empagliflozin [4]. In all cases, treatment with SGLT2 inhibitors significantly reduced the ascites and increased natriuresis was thought to be the main mechanism involved in ascites reduction.

Table 1.

Characteristics of cirrhosis patients with ascites treated with SGLT2 inhibitors

					Laboratory data
Patient	Author	Year	Age (years)/sex	Cause of cirrhosis	s-Alb (g/dL)	s-Cr (mg/dL)	Child–Pugh score	MELD score	Treatment just before SGLT2 inhibitor use
1	Montalvo-Gordon et al. [3]	2020	63/F	NASH	2.8	0.70	>8	10	N.A.
2	Montalvo-Gordon et al. [3]	2020	64/F	NASH	3.5	0.70	>7	9	Insulin (dose N.A.)
3	Kalambokis et al. [4]	2021	54/F	PBC	3.1	0.84	8	12	Linagliptin 5 mg, metformin 1000 mg, insulin glargine 15 units, paracentesis
4	Present case	2021	59/M	Alcoholism	2.6	0.83	10	10	Linagliptin 5 mg, metformin 750 mg, furosemide 20 mg, spironolactone 25 mg

Laboratory data, Child–Pugh score and model for end-stage liver disease (MELD) score were recorded before the administration of the SGLT2 inhibitor. F, female; M, male; s-Alb, serum albumin; s-Cr, serum creatinine; N.A., not available.

SGLT2 inhibitors appear to be well tolerated by patients with reduced liver function [5]. Recent reports, including ours, have shown that SGLT2 inhibitor use is effective for improving ascites and reducing doses of conventional diuretics. We should consider using SGLT2 inhibitors for patients with refractory ascites due to cirrhosis with comorbid type 2 diabetes. Furthermore, SGLT2 inhibitors have been used for heart failure without diabetes [6, 7]. Therefore we plan to study the effects of SGLT2 inhibitors on patients with refractory ascites without diabetes in the future.