Management 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.

Advances in the management of complications from cirrhosis.

Cirrhosis with complications of liver decompensation and hepatocellular carcinoma (HCC) constitute a leading cause of morbidity and mortality worldwide. Portal hypertension is central to the progression of liver disease and decompensation. The most recent Baveno VII guidance included revision of the nomenclature for chronic liver disease, termed compensated advanced chronic liver disease, and leveraged the use of liver stiffness measurement to categorize the degree of portal hypertension. Additionally, non-selective beta blockers, especially carvedilol, can improve portal hypertension and may even have a survival benefit. Procedural techniques with interventional radiology have become more advanced in the management of refractory ascites and variceal bleeding, leading to improved prognosis in patients with decompensated liver disease. While lactulose and rifaximin are the preferred treatments for hepatic encephalopathy, many alternative treatment options may be used in refractory cases and even procedural interventions such as shunt embolization may be of benefit. The approval of terlipressin for the treatment of hepatorenal syndrome (HRS) in the USA has improved the way in which HRS is managed and will be discussed in detail. Malnutrition, frailty, and sarcopenia lead to poorer outcomes in patients with decompensated liver disease and should be addressed in this patient population. Palliative care interventions can lead to improved quality of life and clinical outcomes. Lastly, the investigation of systemic therapies, in particular immunotherapy, has revolutionized the management of HCC. These topics will be discussed in detail in this review.

Management of refractory ascites.

The development of refractory ascites in approximately 10% of patients with decompensated cirrhosis heralds the progression to a more advanced stage of cirrhosis. Its pathogenesis is related to significant hemodynamic changes, initiated by portal hypertension, but ultimately leading to renal hypoperfusion and avid sodium retention. Inflammation can also contribute to the pathogenesis of refractory ascites by causing portal microthrombi, perpetuating the portal hypertension. Many complications accompany the development of refractory ascites, but renal dysfunction is most common. Management starts with continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesisinduced circulatory dysfunction. Albumin infusions independent of paracentesis may have a role in the management of these patients. The insertion of a covered, smaller diameter, transjugular intrahepatic porto-systemic stent shunt (TIPS) in the appropriate patients with reasonable liver reserve can bring about improvement in quality of life and improved survival after ascites clearance. Devices such as an automated low-flow ascites pump may be available in the future for ascites treatment. Patients with refractory ascites should be referred for liver transplant, as their prognosis is poor. In patients with refractory ascites and concomitant chronic kidney disease of more than stage 3b, assessment should be referred for dual liver-kidney transplants. In patients with very advanced cirrhosis not suitable for any definitive treatment for ascites control, palliative care should be involved to improve the quality of life of these patients.

LVP vs TIPS for Refractory Ascites: Where Do We Stand?

AbstractAscites is the most common complication of end stage liver disease. Refractory ascites is considered a poor prognostic indicator and impacts quality of life, overall survival and contributes significantly to the cost associated with its management. Serial large volume paracentesis (LVP) and transjugular intrahepatic portosystemic shunt (TIPS) placement are the most utilized procedures for the management of refractory ascites and have their advantages and disadvantages. The pathophysiology of ascites in cirrhosis is multifactorial which makes management complex, requiring the consideration of multiple clinical and biochemical variables to guide the appropriate management. This article provides a broad overview of LVP and TIPS, with review of the latest clinical trials and meta-analyses to help guide the management of refractory ascites and improve patient outcomes.

A simple nomogram identifies patients with refractory ascites with worse outcome after transjugular intrahepatic portosystemic shunt.

Transjugular intrahepatic portosystemic shunt (TIPS) is increasingly used in the management of refractory ascites. Controversy exists regarding the predictive factors of unfavorable outcomes, useful for patient selection. The primary aim was to identify predictive factors of 1-year survival or recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. The secondary aim was overall survival. Observational, retrospective, multicentric study, that included all cirrhotic patients treated with covered-TIPS for refractory ascites since 2001. Demographic, clinical, laboratory and hemodynamic data were collected at baseline and consecutively until dead, liver transplant or end of follow-up. The Cox model was used to identify predictive factors of overall survival. A Fine-Gray competing risk regression model was used to identify predictive factors of 1-year mortality or recurrent hepatic encephalopathy. A predictive nomogram was created based on those factors. In total 159 patients were included. Predictive factors of survival or recurrent severe encephalopathy were renal dysfunction [hazard ratio, 2.12 (95% CI, 1.11-4.04); P = 0.022], albumin [hazard ratio, 0.58 (95% CI, 0.34-0.97); P = 0.036], serum sodium [hazard ratio, 0.94 (95% CI, 0.89-0.98); P = 0.008] and international normalized ratio [hazard ratio 4.27 (95% CI, 1.41-12.88); P = 0.010]. In the competing risk analysis, predictive factors of 1-year mortality/recurrent severe encephalopathy in multivariate analysis were age [sub-distribution hazard ratio (sHR) 1.05 (95% CI, 1.02-1.09); P = 0.001], creatinine [sHR 1.55 (95% CI, 1.23-1.96); P = 0.001] and serum sodium [sHR 0.94 (95% CI, 0.90-0.99); P = 0.011] at baseline. Age, creatinine and sodium baseline levels strongly influence 1-year survival/recurrent severe hepatic encephalopathy in patients with cirrhosis undergoing covered TIPS for refractory ascites. A simple nomogram accurately and easily identifies those patients with worse prognosis.

Small-diameter TIPS combined with splenic artery embolization in the management of refractory ascites in cirrhotic patients.

Maximally decreasing portal pressures with transjugular intrahepatic portosystemic shunt (TIPS) is associated with improved ascites control but also increased encephalopathy incidence. Since splenic venous flow contributes to portal hypertension, we assessed if combining small-diameter TIPS with splenic artery embolization could improve ascites while minimizing encephalopathy. Fifty-five patients underwent TIPS creation for refractory ascites. Subjects underwent creation of 8 mm TIPS followed by proximal splenic artery embolization (group A, n=8), or of 8 mm (group B, n=6) or 10 mm TIPS (group C, n=41) without splenic embolization. Data were retrospectively reviewed. In group A, median portosystemic gradient decreased from 19 mmHg to 9 mmHg after TIPS, and 8 mmHg after subsequent splenic artery embolization. In groups B and C, gradient decreased from 15 mmHg to 8 mmHg and 16 mmHg to 6 mmHg. All patients except for one in group A and two in C had greater than 50% reduction in the number of paracenteses in 3 months. Any postprocedural encephalopathy incidence was 62%, 50%, 83% in groups A, B, and C, respectively. Overall, 20% of subjects with 10 mm TIPS required TIPS reduction/closure compared to 7% of subjects with 8 mm TIPS. We found that 8 mm diameter TIPS provided similar ascites control compared to 10 mm TIPS regardless of splenic embolization. While more patients with 10 mm TIPS required reduction/closure for severe encephalopathy, the study was underpowered for definitive assessment. Splenic embolization might have the potential to further decrease portosystemic gradient and ascites as an alternative to dilation of TIPS to 10 mm minimizing the risk of encephalopathy, but larger studies are warranted.

A227 UMBILICAL HERNIA INCARCERATION IN LIVER CIRRHOSIS: A RARE COMPLICATION OF PARACENTESIS

Abstract Background Patients with decompensated liver cirrhosis with ascites frequently have umbilical hernias with a prevalence of 20% and are managed with large volume paracentesis (LVP). Common complications of LVP include hemorrhage, infection, and bowel perforation that occur infrequently with a frequency of less than 1%. However, incarceration of umbilical hernias has been reported as a rare complication of LVP and is speculated to be from ascitic fluid decompression that reduces the umbilical hernia ring diameter resulting in entrapment of the hernia sac. It is unclear whether the quantity or the fluid removal rate increases the herniation risk. Based on case series, this rare complication occurs within 48 hours of the LVP and requires emergent surgical repair and involves a high risk of morbidity and mortality due to potential infection, bleeding, and poor wound healing. Aims We describe a case report of an incarcerated umbilical hernia following a bedside large-volume paracentesis. Methods Case report Results A 59-year-old Caucasian male presented to the emergency department with a 24-hour history of acute abdominal pain following his outpatient LVP. His medical history included Child-Pugh class C alcoholic liver cirrhosis with refractory ascites managed with biweekly outpatient LVP and a reducible umbilical hernia. He reported the onset of his abdominal pain 2-hours after his LVP with an inability to reduce his umbilical hernia. Seven liters of clear, straw-coloured asitic fluid was drained. Laboratory values at presentation revealed a hemoglobin of 139 g/L, leukocyte count of 4.9 x109 /L, platelet count of 110 xo 109 /L, and a lactate of 2.7 mmol/L His physical exam demonstrated an irreducible 4 cm umbilical hernia and bulging flanks with a positive fluid wave test. Abdominal computed tomography showed a small bowel obstruction due to herniation of a proximal ileal loop into the anterior abdominal wall hernia, with afferent loop dilation measuring up to 3.4 cm. He was evaluated by the General Surgery consultation service and underwent an emergent laparoscopic hernia repair. There was 5 cm of small bowel noted to be ecchymotic but viable, with no devitalized tissue. He tolerated the surgical intervention with no post-operative complications and was discharged home. Conclusions Ultrasound-guided bedside paracentesis is a common procedure used in the management of refractory ascites and abdominal wall hernia incarceration should be recognized as a potential rare complication. To prevent hernia incarceration, patients with liver cirrhosis should be examined closely for hernias and an attempt should be made for external reduction prior to LVP. A high index of suspicion for this potential life-threatening condition should be had in patients who present with symptoms of bowel obstruction following a LVP. Funding Agencies None

Comparative Study of Slow Infusion versus Bolus Doses of Albumin and Furosemide Infusion to Mobilize Refractory Ascites in Decompensated Chronic Liver Disease.

Combined use of furosemide with albumin is an approved therapy to overcome diuretic resistance in treatment of ascites in decompensated chronic liver disease. Bolus dosing of diuretics has its own limitations due to pre-existing hypotension, post diuretic sodium retention and braking phenomenon. Slow albumin and furosemide Infusion has been shown to mobilize large ascites with improved diuresis and hemodynamic stability in decompensated chronic liver disease. This study was undertaken to compare efficacy and safety of infusion therapy vs bolus therapy in term the management of refractory ascites. Decompensated chronic liver disease patients with refractory ascites were randomly assigned into two groups of 15 each - Bolus therapy (intravenous albumin and furosemide as boluses) and Infusion therapy (furosemide infusion at 2mg/hour and albumin at 2g/hour for three days). Diuresis, natriuresis, change in abdominal girth and body weight, and hemodynamic stability (change in SBP) were compared between the two groups. Infusion therapy, as compared to bolus therapy, showed a significantly better diuresis (mean urinary output increment 483ml vs 243ml, p <0.001), natriuresis (mean urinary sodium excretion increment 35.2 mEq/L vs 16.6 mEq/L, p = 0.004),decrease in abdominal circumference (6.1cm vs 3.0cm, p<0.001) and decrease in body weight (5.53 Kg vs 2.86 Kg, p < 0.001). The complications of renal impairment were also lower in the Infusion group. Infusion of furosemide and albumin is a potential safer and effective therapeutic option in the management of refractory ascites with better natriuresis, higher urine output, and higher decrement in abdominal circumference and body weight, and lesser side effects.

The SALTYFOOD trial: a randomized, controlled trial of home-delivered low-sodium meals for the management of refractory ascites

The SALTYFOOD trial: a randomized, controlled trial of home-delivered low-sodium meals for the management of refractory ascites

A66 GEOGRAPHIC VARIATION AND INCREASED INVOLVEMENT OF INTERVENTIONAL RADIOLOGISTS IN THE MANAGEMENT OF REFRACTORY ASCITES: A POPULATION BASED STUDY

Abstract Background The disease burden from cirrhosis is increasing worldwide. Refractory ascites (RA) is a complication of cirrhosis associated with poor prognosis if liver transplant is not an option. Serial large volume paracentesis (LVP) is the standard of care in the management of refractory ascites (RA) and outpatient LVP has been shown to be safe and cost effective. Epidemiologic data is lacking regarding the incidence of RA, or how patients with RA are managed in routine clinical practice. Aims To describe secular trends in the incidence of RA in Ontario from 2000–2017, and to describe physician provider types performing LVPs in the RA population in Ontario. Methods This retrospective, population-based cohort study uses routinely collected healthcare data from Ontario, Canada, housed at ICES. From January 1, 2000 to Dec 31, 2017 all adult patients with cirrhosis were identified using a validated case definition, and those with RA were identified based on the need for serial LVP. All LVP procedures were described based on patient demographics, local health integration network (LHIN), physician type (Gastroenterology [GI], Internal Medicine [IM], Interventional Radiology [IR], Emergency Medicine [ER], other) and albumin administration. Annual incidence rates (IR) of RA in patients with cirrhosis were calculated and compared using Poisson regression to calculate incident rate ratios (IRRs). Annual LVP volume by provider type and LHIN were calculated and differences were compared using chi-squared analysis. Results The overall incidence of RA in patients with cirrhosis remained relatively stable over the study period (IRR 1.01, 95% CI 1.00–1.02 P&amp;lt;.001). The highest incidence of RA was in those with viral hepatitis and alcohol-related cirrhosis. A total of 90,126 LVPs were identified (median age 61 years [IQR 53–70], 69% male, median LVP per patient 24 [IQR 11–48], 15.8% received albumin infusion). The absolute numbers of LVPs more than tripled over the study period (12,047 in 1997–2002 vs. 37,437 in 2013–2017). GI performed the majority of LVPs (40.1%) followed by IR (22.4%), and IM (8.4%), but there was substantial variation based on location (Fig 1). Overall, the proportion performed by IR increased during the study (7.8% in 1997–2002 vs 30.8% in 2013–2017, P &amp;lt;.001) while the proportion performed by GI decreased (50% 1997–2002 vs 33.1% 2013–2017, P&amp;lt;.001). Conclusions The number of LVPs performed for RA have increased dramatically in Ontario over the past two decades, with the proportion being performed by GI physicians decreasing, while IR is increasing. Substantial variability exists across LHINs on the use of LVP, which may reflect differences in access to resources for LVP, or physician practice. Appropriate albumin use with LVP remains an area for potential quality improvement initiatives in the future. Funding Agencies AASLD Foundation Clinical Translational and Outcomes Research Award in Liver Disease (for supervisor JF)

Safety and Efficacy of Midodrine Hydrochloride in the Management of Refractory Ascites Due to Cirrhosis in Children

Safety and Efficacy of Midodrine Hydrochloride in the Management of Refractory Ascites Due to Cirrhosis in Children

03:45 PM Abstract No. 253 Small-diameter TIPS combined with splenic artery embolization in the management of refractory ascites in cirrhotic patients

03:45 PM Abstract No. 253 Small-diameter TIPS combined with splenic artery embolization in the management of refractory ascites in cirrhotic patients

An update on the pathogenesis and clinical management of cirrhosis with refractory ascites

ABSTRACTIntroduction: Ascites commonly complicates cirrhosis, becoming refractory to treatment with diuretics and sodium restriction in approximately 10% of patients. Pathogenesis of refractory ascites (RA) is multifactorial, the common final pathway being renal hypoperfusion and avid sodium retention. Refractory ascites has a negative prognostic implication in the natural history of cirrhosis. Management of RA include sodium restriction and regular large volume paracentesis (LVP) with albumin infusions, preventing paracentesis-induced circulatory dysfunction. In appropriate setting, transjugular intrahepatic porto-systemic shunt (TIPS) can be considered. Ascites clearance with TIPS can lead to nutritional improvement, avoiding sarcopenia. Liver transplantation (LT) remains the definitive treatment for eligible candidates.Areas covered: Our review summarizes current updates on pathogenesis and clinical management of RA including potential future therapeutic options such as the automated slow-flow ascites pump, chronic outpatient albumin infusion and cell-free and concentrated ascites reinfusion therapy.Expert commentary: Standard of care in patients with RA include LVP with albumin replacement and prompt referral for LT where indicated. Other novel therapeutic options on the horizon include automated low-flow ascites pump and cell-free, concentrated albumin reinfusion therapy.

Usefulness of cell-free and concentrated ascites reinfusion therapy in the therapeutic management of advanced ovarian cancer patients with massive ascites.

The management of refractory ascites in advanced ovarian cancer (AOC) is vital for patients with abdominal distention, respiratory distress, and anorexia due to massive ascites with cancer peritonitis. We analyzed the benefits of concentrated ascites reinfusion therapy (CART) in the management of AOC. We reviewed records of AOC patients who underwent CART between January 2011 and March 2017. We retrospectively analyzed patients' backgrounds and physiological changes, including body weight, abdominal girth, urine volume, blood component values, blood pressure, heart rate, and body temperature before and after CART. We investigated the clinicopathological significance of CART by measuring the mean number of ascites tumor cell (ATC) clusters before CART. A retrospective analysis was performed on 29 cases of AOC with massive ascites involving 47 CART sessions. The patients' mean age was 56.6 ± 12.8 years, and the mean number of sessions was 1.7 ± 1.2. The mean volume of the processed ascites was 2,937 ± 820mL, which was concentrated to 272 ± 84mL containing 85.0 ± 33.2g protein on average. Significant reductions in abdominal girth (- 5.30 ± 0.65cm; p < 0.0001) and body weight (- 2.97 ± 0.26kg; p = 0.0011), increased urine volume (+ 824.29 ± 145.21mL; p < 0.0001), and improved serum albumin levels (+ 0.18 ± 0.34; p < 0.0001) were observed after CART. Analysis of variance revealed significant elevations in body temperature after CART in 11 patients with a small number of ATC clusters. CART is useful for the therapeutic management of AOC patients with refractory massive ascites. Elevations of body temperature after CART may be avoided by the investigation of patients' peritoneal cytology before CART.

Management of refractory ascites by a Denver peritoneo-venous shunt after kidney transplantation in a patient with autosomal dominant polycystic kidney disease

Management of refractory ascites by a Denver peritoneo-venous shunt after kidney transplantation in a patient with autosomal dominant polycystic kidney disease

Transjugular Intrahepatic Portosystemic Shunt Using the Trans-splenic Approach and a Snare Technique

AbstractTransjugular intrahepatic portosystemic shunt (TIPS) is an established procedure for the secondary prevention of variceal bleeding and management of refractory ascites. Portal vein thrombosis presents technical difficulty during TIPS due to nonvisualization of portal vein. In such patients, trans-splenic approach can be utilized to navigate thrombosed portal vein and use a snare as a fluoroscopic guidance for the intraparenchymal pass. We present the case of a 63-year old man who received the successful TIPS procedure via trans-splenic access without any complication.

PWE-147 Nurse Led Day Case Paracentesis

IntroductionRefractory ascites is a debilitating condition. Prior to the implementation of nurse led day case paracentesis all patients were admitted into the hospital for an inpatient stay of between 3...

Incarcerated Umbilical Hernia as an Immediate Complication of Large Volume Paracentesis

Purpose: Therapeutic paracentesis is a common procedure used in the management of refractory ascites in patients with cirrhosis. The procedure, while generally simple and safe, has known complications such as bleeding, viscus perforation and metabolic disturbances. We present a rare complication of therapeutic paracentesis: immediate post-procedure incarcerated umbilical hernia. A 57-year-old woman with alcoholic cirrhosis (Child's classification B) was admitted to ambulatory surgery unit for an elective paracentesis. She had massive ascites and a 6-cm umbilical hernia filled with fluid. Seven liters of clear, straw-colored fluid were removed with a 14-gauge needle, and this appeared to be a total paracentesis. She was given 50 grams of salt-poor albumin and prepped for discharge. After standing and dressing for discharge, the patient developed abdominal pain and distension. On examination, it was obvious that she had gas-filled bowel loops in a hernia that could not be reduced (figure). Abdomen was tympanic, consistent with bowel obstruction. Surgical consult was obtained and she underwent reduction and repair of the umbilical hernia, which she tolerated well. Elective repair of umbilical hernias in patients with cirrhosis is usually frowned upon, as hernia recurrence is common unless the ascites can be controlled with diuretics. In addition, this patient group is generally a poor surgical risk due to infection, bleeding and poor wound healing. However, there was not an option in this case, as the hernia presented acutely. Incarceration can occur due to a decrease in tension in the umbilical ring following large volume paracentesis. It may be reasonable to consider TIPS in patients with a significant umbilical hernia whose ascites cannot be controlled with diuretics and whose hernia size runs a risk of incarceration. At the very least, clinicians should be aware of this complication and evaluate patients complaining of pain and distention after paracentesis to rule out this life-threatening condition and be prepared to act quickly to avoid poor outcomes in this compromised group of patients.Figure

207 DIAGNOSTIC PERFORMANCE OF C-REACTIVE PROTEIN AND NEUTROPHIL-TO-LYMPHOCYTE RATIO FOR INFECTION IN PATIENTS WITH DECOMPENSATED CIRRHOSIS

TIPS in Korea based on a multicenter retrospective study. Methods: The authors retrospectively reviewed the medical records of 59 patients who underwent TIPS for refractory ascites with liver cirrhosis from 2000 to 2012 in Korea. Results: TIPS was successfully in all 59 patients. Of these, we review medical records of the 55 patients. Complication of the procedure is bleeding (2 patients), hypotension of the unknown origin (1 patient), aggravated heart failure (1 patient). Stent dysfunction happened 5 patients due to stent stenosis (4 patients), stent thrombosis (1 patient) during follow up. Mean follow up period was 326 days. During follow up, 50 (90.9%) patients died and only 2 patients had liver transplantation. 5 (9.1%) patients had shunt revision due to stent dysfunction. The probability of survival without liver transplantation was 26.5% at 1 year. 1-month mortality was 29.1%. The response was assessed in patients who were alive, without transplanstation, at each time point. Either complete or partial response of the ascites was obtained in 68.6%, 75.0 %, 76.4% and 69.2% at 1, 3, 6, 12 months, respectively. Mortality was 29.1%, 48.3%, 58.2% and 70.9% at 1, 3, 6, 12 months, respectively. In 15 patients (30%), a new episode of encephalopathy developed or aggravated and 12 patients (80%) were grade III or IV but most of them (9 patients, 75%) responded quickly to treatment. Conclusions: TIPS is a reliable option or bridge therapy prior to liver transplantation for the management of refractory ascites in patients with liver cirrhosis.

MANAGEMENT OF ASCITES IN CIRRHOSIS

Ascites is a common complication of liver cirrhosis associated with a poor prognosis. The treatment of ascites requires dietary sodium restriction and the judicious use of diuretics. Management of refractory ascites in cirrhosis requires treatments of repeat largevolumeparacentesis (LVP) or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS), and assessment for liver transplantation. Potential new treatment options for ascites include the use of various vasoconstrictors, vasopressin V 2 receptor antagonists, or the insertion of a peritoneo-vesical shunt.