The Chinese Society of Hepatology developed the current guidelines for the Management of Ascites and Its Related Complications in Cirrhosis based on the published evidences and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of cirrhotic ascites emphasizing a step-wise approach with the first-, second-, and third-line therapy. For refractory ascites, vasoconstrictors and albumin are recommended for splanchnic vasodilation and selective vasopressin (V2) receptor antagonists for moderate-to-severe hyponatremia. For spontaneous bacterial peritonitis, empirical anti-infection treatment was recommended based on the local microbiological examination of community- or hospital-acquired infections. For hepatorenal syndrome, the administration of vasopressor terlipressin and albumin is recommended.

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Chinese guidelines on the management of ascites and its related complications in cirrhosis

This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords: "liver cirrhosis," "portal hypertension," "ascites," "pathogenesis," "diagnostics," and "treatment." Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.

Current approaches to the management of patients with cirrhotic ascites.

Among the various risky complications of liver cirrhosis, refractory ascites is associated with poor survival of cirrhotics and persistently worsens their quality of life (QOL). Major clinical guidelines worldwide define refractory ascites as ascites that cannot be managed by medical therapy either because of a lack of response to maximum doses of diuretics or because patients develop complications related to diuretic therapy that preclude the use of an effective dose of diuretics. Due to the difficulty in receiving a liver transplantation (LT), the ultimate solution for refractory ascites, most cirrhotic patients have selected the palliative therapy such as repeated serial paracentesis, transjugular intrahepatic portosystemic shunt, or peritoneovenous shunt to improve their QOL. During the past several decades, new interventions and methodologies, such as indwelling peritoneal catheter, peritoneal-urinary drainage, and cell-free and concentrated ascites reinfusion therapy, have been introduced. In addition, new medical treatments with vasoconstrictors or vasopressin V2 receptor antagonists have been proposed. Both the benefits and risks of these old and new modalities have been extensively studied in relation to the pathophysiological changes in ascites formation. Although the best solution for refractory ascites is to eliminate hepatic failure either by LT or by causal treatment, the selection of the best palliative therapy for individual patients is of utmost importance, aiming at achieving the longest possible, comfortable life. This review briefly summarizes the changing landscape of variable treatment modalities for cirrhotic patients with refractory ascites, aiming at clarifying their possibilities and limitations. Evolving issues with regard to the impact of gut-derived systemic and local infection on the clinical course of cirrhotic patients have paved the way for the development of a new gut microbiome-based therapeutics. Thus, it should be further investigated whether the early therapeutic approach to gut dysbiosis provides a better solution for the management of cirrhotic ascites.

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Management of refractory cirrhotic ascites: challenges and solutions

CART: Cell-free and Concentrated Ascites Reinfusion Therapy against malignancy-related ascites

Objective Hyponatremia is closely associated with the pathophysiology of cirrhosis. However, the association between the serum sodium level and the response to tolvaptan is unclear. This study evaluated the factors related to the tolvaptan response and the prognosis in cirrhosis patients with ascites and hyponatremia. Methods We retrospectively reviewed the clinical records of cirrhosis patients hospitalized for treatment with tolvaptan. The associations of patient baseline characteristics with the tolvaptan response after one week and of the characteristics after one-month tolvaptan treatment with the prognosis were analyzed. Results We analyzed 83 cirrhosis patients with ascites, including 34 patients with hyponatremia. The response rates to tolvaptan in patients with serum sodium 135 mEq/L were 20%, 66%, and 58%, respectively (p=0.22). The serum sodium level was associated with the response to tolvaptan [odds ratio=1.18; 95% confidence interval (CI) =1.02-1.37; p=0.029]. In patients with hyponatremia, the serum sodium level after 1-month tolvaptan treatment was increased compared to baseline (132 mEq/L vs. 136 mEq/L, p=0.006), and an increasing serum sodium level was associated with a lower risk of mortality (hazard ratio=0.85; 95% CI=0.75-0.97; p=0.016). The survival rate was higher in patients with an increase in the serum sodium level after 1 month than in patients with a decreased serum sodium level (p=0.023). Conclusion Tolvaptan treatment was effective in cirrhosis patients with ascites and hyponatremia, but a low serum sodium level was associated with non-responsiveness to tolvaptan. An increased serum sodium level after one-month tolvaptan treatment may positively influence the mortality risk in cirrhosis patients with hyponatremia.

Association between the Serum Sodium Levels and the Response to Tolvaptan in Liver Cirrhosis Patients with Ascites and Hyponatremia

Cell-free and concentrated ascites reinfusion therapy (CART) is expected to improve symptoms associated with refractory ascites of the decompensated liver cirrhosis patients. The aim of this study was to evaluate the safety and efficacy of the CART system performed on the decompensated liver cirrhosis patients. In this retrospective observational study, we evaluated 24 CART processes performed on 11 patients with decompensated liver cirrhosis. We evaluated the effectiveness and adverse events during CART procedures. The amounts of collected and concentrated ascites were 4491.7 ± 2222.8 mL (mean ± SD), respectively, and the concentration ratio was 22.4 ± 15.3 times, respectively. The amount of collected protein in ascites was 2.3 ± 0.5 g/dL, and concentration ratio of protein was 8.2 ± 9.4 times. Serum protein level was not significantly different between before and after CART sessions. Thus, CART allowed for the reduction of doses of albumin preparations (Alb) to be administered. CART has been reported to cause two adverse reactions: elevation of body temperature and decrease in blood pressure. In our study, decreased blood pressure was not observed even in patients with > 5 L of ascites drained. Although a transient elevation in body temperature was seen in only one patient, this febrile patient immediately returned to normal body temperature with the use of NSAIDs. In patients with refractory ascites of decompensated liver cirrhosis in whom complete cure cannot be expected, CART improves their QOL and, in terms of medical economy, allows for the reduction of doses of Alb. CART can be effectively applied as a palliative procedure for refractory ascites of decompensated liver cirrhosis patients.

Masahiro IInuma

Papers

Cell-Free and Concentrated Ascites Reinfusion Therapy for Decompensated Liver Cirrhosis.