Treatment Of Refractory Ascites Research Articles

Update on Tolvaptan for the Treatment of Refractory Ascites in Liver Cirrhosis

Ascites is the most prevalent complication of decompensated cirrhosis, and approximately 5%-10% of cirrhotic ascites will develop into refractory ascites (RA). With complicated pathogenesis, obscure treatment strategies and poor prognosis, it is still a challenge for physicians to manage RA properly. Tolvaptan (TLV) is a new type of non-peptide selective arginine vasopressin V2 receptor antagonist targeting at suppressing renal water reabsorption, promoting free water excretion and raising blood sodium levels, which provides a new option for the treatment of RA in liver cirrhosis. In this review, we summarized the mechanisms of TLV's effect and described its efficacy, safety and predictive factors of response in treating RA, intending to provide a supplement for clinical application of tolvaptan in the management of RA.

Palliative long-term abdominal drains vs large volume paracenteses for the management of refractory ascites in end-stage liver disease.

Long-term abdominal drains (LTAD) are a cost-effective palliative measure to manage malignant ascites in the community, but their use in patients with end-stage chronic liver disease and refractory ascites is not routine practice. The safety and cost-effectiveness of LTAD are currently being studied in this setting, with preliminary positive results. We hypothesised that palliative LTAD are as effective and safe as repeat palliative large volume paracentesis (LVP) in patients with cirrhosis and refractory ascites and may offer advantages in patients' quality of life. To compare the effectiveness and safety of palliative LTAD and LVP in refractory ascites secondary to end-stage chronic liver disease. A retrospective, observational cohort study comparing the effectiveness and safety outcomes of palliative LTAD and regular palliative LVP as a treatment for refractory ascites in consecutive patients with end-stage chronic liver disease followed-up at our United Kingdom tertiary centre between 2018 and 2022 was conducted. Fisher's exact tests and the Mann-Whitney U test were used to compare qualitative and quantitative variables, respectively. Kaplan-Meier survival estimates were generated to stratify time-related outcomes according to the type of drain. Thirty patients had a total of 35 indwelling abdominal drains and nineteen patients underwent regular LVP. The baseline characteristics were similar between the groups. Prophylactic antibiotics were more frequently prescribed in patients with LTAD (P = 0.012), while the incidence of peritonitis did not differ between the two groups (P = 0.46). The incidence of acute kidney injury (P = 0.014) and ascites/drain-related hospital admissions (P = 0.004) were significantly higher in the LVP group. The overall survival was similar in the two groups (log-rank P = 0.26), but the endpoint-free survival was significantly shorter in the LVP group (P = 0.003, P < 0.001, P = 0.018 for first ascites/drain-related admission, acute kidney injury and drain-related complications, respectively). The use of LTAD in the management of refractory ascites in palliated end-stage liver disease is effective, safe, and may reduce hospital admissions and utilisation of healthcare resources compared to LVP.

Nutritional status in hepatic encephalopathy and transjugular intrahepatic portosystemic shunt - TIPS, and strategies to improve the outcomes.

Hepatic encephalopathy (HE) is one of the most severe complications following transjugular intrahepatic portosystemic shunt (TIPS). The identification and treatment of risk factors associated with the development of this complication may reduce the incidence and severity of post-TIPS HE. Several studies have demonstrated that the nutritional status plays a major role in the outcome of the cirrhotic population, particularly those who are decompensated. Although scarce, there are also studies highlighting an association between poor nutritional status, sarcopenia, fragile status, and post-TIPS HE. If these data are confirmed, nutritional support could become a means for decreasing this complication, thereby enhancing the use of TIPs in the treatment of refractory ascites or variceal bleeding. In this review, we will discuss the pathogenesis of HE, the data that supports an association with sarcopenia, nutritional status and frailty and the implications that these conditions have on the use of TIPS in clinical practice.

Occurrence of fever in cell-free and concentrated ascites reinfusion therapy is not related to the primary disease or nature of ascites.

Cell-free and concentrated ascites reinfusion therapy (CART) is a treatment for refractory ascites wherein filtered and concentrated ascitic fluid is reinfused. Although fever is one of the side effects of CART, its cause is not clear. Patients who underwent at least one CART session between June 2011 and May 2021 at our medical center were retrospectively enrolled in the study. They were classified according to the primary disease and nature of ascites. Ninety patients were included in this study. Increase in body temperature (BT) after CART was observed, regardless of the primary disease and nature of ascites. The difference in temperature before and after CART did not differ based on the primary disease [cancerous (including hepatocellular carcinoma, ovarian cancer) and non-cancerous] and nature of ascites. Elevated BT and fever after CART are not related to the primary disease and nature of the ascites.

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

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.

Treatment of refractory ascites: Current strategies and new landscape of non-selective beta-blockers

Ascites is the fluid accumulation in the peritoneal cavity, and it is the consequence of a wide variety of entities, being liver cirrhosis the most common one. In this kind of patients, the development of ascites results from splanchnic vasodilation; decreased effective circulating volume; the activation of the sympathetic nervous system and the renin–angiotensin–aldosterone system; and a systemic inflammatory process. Its management is diverse and depends on the severity of the hemodynamic disturbance and other clinical manifestations. In recent years, therapeutic strategies have been developed, but they tend to result unconventional, so new evidence demonstrates the advantages of non-selective beta-blockers for the survival rate of patients with end-stage cirrhosis and ascites. La ascitis es la acumulación de líquido en la cavidad peritoneal, y es consecuencia de una amplia variedad de entidades, siendo la cirrosis la más frecuente. En este tipo de pacientes, el desarrollo de ascitis resulta de la vasodilatación esplácnica, el volumen circulante efectivo disminuido, la activación del sistema nervioso simpático y el sistema renina-angiotensina-aldosterona, así como un proceso inflamatorio sistémico. Su tratamiento es diverso, y depende de la gravedad de la alteración hemodinámica y otras manifestaciones clínicas. En años recientes se han desarrollado estrategias terapéuticas poco convencionales, así como nueva evidencia demuestra los beneficios de los betabloqueadores no selectivos en la tasa de supervivencia de los pacientes con cirrosis en etapa terminal y ascitis.

S1267 The Use of Prophylactic Treatment in the Prevention of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt

Introduction: Transjugular intrahepatic portosystemic shunt (TIPS) procedures are indicated in the treatment of refractory ascites or variceal bleeding in patients with end-stage liver disease. Hepatic encephalopathy (HE) is a major complication of the procedure as ammonia is able to bypass the liver. Previous studies have shown prophylactic use of rifaximin to have significant benefit in primary prevention of HE. The purpose of our study was to evaluate how frequently primary HE prophylaxis medications were prescribed and to assess if this led to decreased incidence of HE. Methods: We performed a retrospective chart review of 231 patients who received TIPS over the past 10 years at our institution that also had at least one follow up visit. Patient demographics were recorded including age, race, cirrhosis etiology, cirrhotic decompensations, MELDNa, BMI, pre/post TIPS gradients, and use of HE prophylaxis medications. Diagnosis of hepatic encephalopathy was performed through chart review by reviewing both Hepatology clinic notes and all hospital admissions. Variables were analyzed using Chi-Squared test, two sample T test, and multivariate analysis for incidence of hepatic encephalopathy. Results: Our cohort included 231 patients with 95 females (41.1%) and the majority being elective cases (62.8%). Common indications for TIPS included esophageal varices (51.9%), ascites (35.5%), and hepatic hydrothorax (7.8%). There were 111 patients that were discharged with lactulose, 9 patients discharged with rifaximin, 55 patients discharged with a combination of lactulose and rifaximin, and 57 patients were discharged without HE prophylaxis. Multivariate analysis showed the incidence of HE was significantly reduced in the group of patients discharged with lactulose [Adjusted Odds Ratio (OR): 0.48, 95% CI (0.23-0.99), p=0.049] and a near significant difference in patients discharged with a combination of lactulose and rifaximin [Odds Ratio (OR): 0.48, 95% CI (0.20-1.15), p=0.100]. (Table) Conclusion: Lactulose as prophylaxis following TIPS procedure was associated with significantly decreased likelihood of developing HE. Lactulose provides a cost effective alternative to rifaximin. Table 1. - Variable Unadjusted OR 95% CI p-value Adjusted OR 95% CI p-value Age 1.019 0.993, 1.045 0.1482 1.027 0.997, 1.058 0.0781 BMI 0.994 0.959, 1.030 0.7428 0.998 0.959, 1.038 0.9097 Pre-TIPS Gradient 1.009 0.954, 1.068 0.7515 0.977 0.906, 1.053 0.5428 Post-TIPS Gradient 1.079 0.970, 1.200 0.1616 1.076 0.937, 1.236 0.2967 Gradient Change 1.016 0.953, 1.082 0.6283 NA Gender Female ref ref Male 1.459 0.854, 2.493 0.1664 1.300 0.700, 2.413 0.4066 Ethnicity White ref ref Black 0.491 0.169, 1.426 0.1908 0.373 0.105, , 1.322 0.1265 Other 0.510 0.097, 2.689 0.4274 0.388 0.0622.428 0.3115 TIPS Indication EV ref ref Ascites 0.692 0.388, 1.234 0.2118 0.599 0.285, 1.261 0.1775 Hydrothorax 1.011 0.373, 2.741 0.9823 1.130 0.369, 3.462 0.8301 Volume Overload NC Prior HE No ref ref Yes 0.810 0.4411.489 0.4971 1.380 0.636, 2.992 0.4147 Unknown 0.634 0.1832.190 0.4710 0.804 0.186, 3.469 0.7699 Prior Hep Visit No ref ref Yes 1.103 0.619, 1.966 0.7390 1.064 0.5042.245 0.8701 HE Prophylaxis Meds None ref ref Lactulose 0.491 0.257, 0.939 0.0316 0.484 0.235, 0.996 0.0486 Rifaximin 1.048 0.255, 4.313 0.9478 1.326 0.234, 7.503 0.7495 Both 0.518 0.244, 1.100 0.0871 0.476 0.197, 1.153 0.1000 Surgery Elective ref ref Emergent 1.483 0.867, 2.538 0.1503 1.523 0.729, 3.180 0.2632

Treatment of refractory ascites with an automated low flow ascites pump in patients awaiting liver transplantation

BackgroundFor patients with liver cirrhosis awaiting liver transplantation who suffer from refractory ascites (RA), standard treatment consists of repeated large volume paracentesis. The automated low-flow ascites-pump (alfapump) offers an innovative treatment alternative for patients with RA, if TIPSS is contraindicated or ineffective. This study addresses the feasibility of alfapump treatment in patients awaiting liver transplantation. MethodsBetween 2012 and 2018, patients listed for liver transplantation who were treated with an alfapump were included in this retrospective single centre study. ResultsOf 22 patients listed for liver transplantation and treated with an alfapump, 14 were finally transplanted. Alcohol-related liver disease was the most common aetiology for liver cirrhosis (n = 11), followed by hepatitis C, hepatitis B and NASH. Mean age at listing was 56.3 years and 68.2% of patients were male. The average daily ascites volume pumped by the device was 1076 ml. During transplant surgery, no alfapump-related complications occurred. The alfapump was removed at the end of the transplant procedure in eight patients and left in place in three patients for up to 104 days, whereas three patients had the pump removed prior to the transplantation. Overall survival was significantly better in patients that were finally transplanted (log-rank p < 0.0001). Five patients (22.7%) required at least one alfapump-related re-intervention. ConclusionTreatment with an alfapump in patients on the liver transplant waiting list with refractory ascites is feasible. The alfapump did not affect the transplant procedure and was explanted in most patients at the end of the transplant surgery.

Surgical versus medical treatment of refractory ascites

Surgical versus medical treatment of refractory ascites

Rifaximin improves survival in cirrhotic patients with refractory ascites: A real-world study.

BACKGROUNDRifaximin has been shown to reduce the incidence of hepatic encephalopathy and other complications in patients with cirrhosis. However, few studies have investigated the effect of rifaximin in cirrhotic patients with refractory ascites.AIMTo evaluate the effects of rifaximin in the treatment of refractory ascites and to preliminarily explore its possible mechanism.METHODSA total of 75 cirrhotic patients with refractory ascites were enrolled in the study (50 in a rifaximin and 25 in a control group). Patients in the rifaximin group were divided into two subgroups according to the presence of spontaneous bacterial peritonitis and treatment with or without other antibiotics (19 patients treated with rifaximin and 31 patients treated with rifaximin plus intravenous antibiotics). All patients received conventional treatment for refractory ascites, while patients in the rifaximin group received oral rifaximin-α 200 mg four times daily for at least 2 wk. The ascites grade, fasting weight, liver and kidney function, and inflammatory factors in the plasma were evaluated before and after treatment. In addition, the gut microbiota was determined by metagenomics sequencing to analyse the changes in the characteristics of the gut microbiota before and after rifaximin treatment. The patients were followed for 6 mo.RESULTSCompared with the control group, the fasting weight of patients significantly decreased and the ascites significantly subsided after treatment with rifaximin (P = 0.011 and 0.009, respectively). The 6-mo survival rate of patients in the rifaximin group was significantly higher than that in the control group (P = 0.048). The concentration of interferon-inducible protein 10 decreased significantly in the rifaximin group compared with that in the control group (P = 0.024). The abundance of Roseburia, Haemophilus, and Prevotella was significantly reduced after rifaximin treatment, while the abundance of Lachnospiraceae_noname, Subdoligranulum, and Dorea decreased and the abundance of Coprobacillus increased after treatment with rifaximin plus intravenous antibiotics. The gene expression of virulence factors was significantly reduced after treatment in both subgroups treated with rifaximin or rifaximin plus intravenous antibiotics.CONCLUSIONRifaximin mitigates ascites and improves survival of cirrhotic patients with refractory ascites. A possible mechanism is that rifaximin regulates the structure and function of intestinal bacteria, thus improving the systemic inflammatory state.

Management of refractory ascites attenuates muscle mass reduction and improves survival in patients with decompensated cirrhosis.

This study investigated time-course changes in skeletal muscle volume per year with tolvaptan in patients with refractory ascites that was unresponsive to loop diuretics and aldosterone antagonists. This retrospective study included 42 patients who received tolvaptan for refractory ascites and/or hepatic edema and underwent computed tomography (CT) before and ≥3months after initiating tolvaptan. The time-course changes in skeletal muscle index per year [ΔSMI (%)] was calculated as follows: ΔSMI (%)=(SMI at final CT scan - SMI at initial CT scan)/SMI at initial CT scan×100/years between CT scans. Eligible patients were 23 men and 19 women of median age of 71years (range 21-94years). The median follow-up period was 22.7 (range 3.5-54.6) months. ΔSMI (%) was significantly higher in the responders group than in the nonresponder group. Multivariate analysis showed the response to tolvaptan was an independent and significant factor associated with an increase in muscle mass [odds ratio (OR) 20.364; 95% CI 2.327-178.97; P=0.006]. Overall survival with tolvaptan was significantly higher in the responder group than in the nonresponder group. Multivariate analysis showed that the response to tolvaptan treatment was a significant contributor to good prognosis (OR 3.884; 95% CI 1.264-11.931; P=0.018). A significant negative correlation was observed between the dosage of furosemide and ΔSMI (%) (P=0.014). Treatment of refractory ascites with tolvaptan may attenuate the progression of sarcopenia and improve the prognosis in patients with decompensated cirrhosis.

Miniature Pump for Treatment of Refractory Ascites Based on Local Magnetic Actuation

This paper presents the design, fabrication, and experimental validation of a novel low-cost implantable pump for the treatment of refractory ascites (RA) based on local magnetic actuation (LMA). A reciprocating positive displacement pump displaces liquid unidirectionally through magnetic coupling with a magnetic controller placed on the outside of the patient's body. The proposed solution is intuitive to use given an alignment algorithm that exploits externally placed magnetic field sensors (MFS). The implantable device has a catheter-like shape, is electronic free (no on-board battery), has low fabrication cost (&lt;8 USD), and is able to generate a flow-rate of 3.65 L/h while effectively pumping fluids with various viscosity (1–5.5 cP). RA is commonly treated via costly paracentesis or invasive surgical placement of a transjugular portosystemic shunt (TIPS). The proposed solution can be implanted with minimally invasive techniques and can be used on a daily basis to drain a set amount of liquid, without requiring recurrent hospital visits.

Prognosis of patients with ascites after PleurX insertion: an observational study

Objective: To evaluate the safety of PleurX in cirrhotic patients with refractory ascites.Methods: We prospectively registered patients who received a PleurX catheter cirrhosis-associated refractory ascites at our department from July 2015 to November 2016. Our control group consisted of matched cirrhotic patients with refractory ascites treated with large volume paracentesis (LVP) and patients with malignant ascites treated with PleurX during the same period.Results: We included 25 patients with cirrhosis-related ascites (7 in PleurX group) and 17 with malignant ascites (14 in PleurX group). Of these, six patients had hepatocellular carcinoma and cirrhosis (5 in PleurX group). None were eligible for insertion of a TIPS or liver transplantation. The maximum duration of follow-up was (480 days) in the PleurX group and 366 days in the LVP group (median 84 and 173 days, respectively). There was no difference in mortality when comparing PleurX with LVP treatment (hazard ratios: 3.0 and 1.0, p = .23 and .96, respectively). Mortality was higher in patients with malignant ascites (p= .01). We found no significant differences in adverse events (incl. spontaneous bacterial peritonitis) or in P-albumin, P-creatinine and P-sodium between the groups.Conclusion: PleurX insertion for the treatment of refractory ascites in cirrhotic patients appears to be safe. Prospective randomized trials are necessary in order to confirm these findings.

Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis.

SummaryBackgroundRefractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low‐flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.AimTo assess safety and efficacy of this treatment in patients with a contraindication to TIPSS.MethodsFifty‐six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded.ResultsAt the time of this analysis, 3 patients completed the 24‐month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty‐three pump‐related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow‐up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month.ConclusionsThe alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions. https://clinicaltrials.gov/ct2/show/NCT01532427

EPTFE-TIPS versus repetitive LVP plus albumin for the treatment of refractory ascites in patients with cirrhosis

ePTFE-TIPS versus repetitive LVP plus albumin for the treatment of refractory ascites in patients with cirrhosis

New therapeutic paradigm and concepts for patients with cirrhotic refractory ascites

The activation of renin-angiotensin-aldosterone-vasopressin system is a key factor in the formation of ascites due to splanchnic vasodilation in cirrhosis. In theory, aldosterone antagonists, contraction of blood vessels, vasopressin V2 receptor, and angiotensin receptor antagonists are important targets for the prevention and treatment of cirrhotic ascites. The 15%-20% of patients with cirrhotic ascites that show no response to at least one week's treatment with potent diuretics (spironolactone 160 mg/d combined with furosemide 80 mg/d) are considered to have refractory ascites. At present, effective treatments for refractory ascites include tolvaptan, large-volume paracentesis (4000-6000 ml/time/day) combined with albumin (4 g/L ascites), ascites ultrafiltration and reinfusion, transjugular intrahepatic portosystemic shunt, and liver transplantation. In the future, with the development of vasoactive drugs, rifaximin, ascites drainage pump, and other new therapies, the treatment of refractory ascites may be more effective to reduce the need for liver transplantation.

Combined treatment of refractory ascites by alfapumpTM and surgical umbilical hernia repair in cirrhotic patients: Is this the right paradigm?

Combined treatment of refractory ascites by alfapumpTM and surgical umbilical hernia repair in cirrhotic patients: Is this the right paradigm?

Transjugular intrahepatic portosystemic shut vs total paracentesis for treatment of refractory ascites in patients with cirrhosis: A meta-analysis

Transjugular intrahepatic portosystemic shut <i>vs</i> total paracentesis for treatment of refractory ascites in patients with cirrhosis: A meta-analysis

Progress in treatment of liver cirrhosis with ascites

Ascites formation represents a hallmark of decompensated liver cirrhosis. It predicts a poor outcome. Patients with ascites are at high risk of developing complications such as SBP (spontaneous bacterial peritonitis), hyponatremia and HRS (hepatorenal syndrome). Adequate treatment of cirrhotic ascites increases survival and betters quality of life. Despite improved current medical treatment of ascites, liver transplantation remains the ultimate treatment of refractory ascites. This paper summarizes the treatment of liver cirrhosis with ascites. Key words: Liver cirrhosis/CO/TH; Ascites/CO/TH; Review

Treatment for cirrhotic ascites

Common complications of decompensated liver cirrhosis are esophageal varices, hepatic encephalopathy and ascites. After the onset of complications, the prognosis worsens. In patients with ascites, the 5-year mortality rate is 44%. Furthermore, hyponatremia, spontaneous bacterial translocation and hepatorenal syndrome also greatly worsen the prognosis. Effective treatment of cirrhotic ascites improves the quality of life and survival rate. Recently, the newly produced diuretic, tolvaptan (vasopressin V2 receptor antagonist), was reported to be effective in the treatment of refractory ascites in liver cirrhosis; however, there has not been an associated positive effect on the prognosis. There are various types of treatment for ascites, such as large-volume paracenteses, a cell-free and concentrated ascites reinfusion therapy, a transjugular intrahepatic portosystemic shunt, and a peritoneo-venous shunt. Although they improve the prognosis, liver transplantation remains the ultimate form of treatment. The present article discusses the therapeutic management of cirrhotic ascites.