Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases

HepatologyVolume 74, Issue 2 p. 1014-1048 Practice GuidanceFree Access Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases Scott W. Biggins, Corresponding Author Scott W. Biggins bigginss@medicine.washington.edu Division of Gastroenterology and Hepatology, and Center for Liver Investigation Fostering discovEry, University of Washington, Seattle, WA ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Scott W. Biggins, M.D., M.A.S.13324 Division of Gastroenterology and Hepatology and Center for Liver Investigation Fostering discovEry, University of Washington 1959 NE Pacific Street, Box 356175 Seattle, WA 97195 E-mail: bigginss@medicine.washington.edu Tel.: 206-598-1908Search for more papers by this authorPaulo Angeli, Paulo Angeli Unit of Hepatic Emergencies and Liver Transplantation, Department of Medicine, DIMED, University of Padova, Padua, ItalySearch for more papers by this authorGuadalupe Garcia-Tsao, Guadalupe Garcia-Tsao Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT VA-CT Healthcare System, West Haven, CTSearch for more papers by this authorPere Ginès, Pere Ginès orcid.org/0000-0003-4657-4504 Liver Unit, Hospital Clinic, and Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain Centro de Investigación Biomèdica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainSearch for more papers by this authorSimon C. Ling, Simon C. Ling The Hospital for Sick Children, Division of Gastroenterology, Hepatology and Nutrition, and Department of Paediatrics, University of Toronto, Toronto, Ontario, CanadaSearch for more papers by this authorMitra K. Nadim, Mitra K. Nadim Division of Nephrology, University of Southern California, Los Angeles, CASearch for more papers by this authorFlorence Wong, Florence Wong orcid.org/0000-0001-9263-8869 Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, CanadaSearch for more papers by this authorW. Ray Kim, W. Ray Kim orcid.org/0000-0002-3030-860X Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CASearch for more papers by this author Scott W. Biggins, Corresponding Author Scott W. Biggins bigginss@medicine.washington.edu Division of Gastroenterology and Hepatology, and Center for Liver Investigation Fostering discovEry, University of Washington, Seattle, WA ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO: Scott W. Biggins, M.D., M.A.S.13324 Division of Gastroenterology and Hepatology and Center for Liver Investigation Fostering discovEry, University of Washington 1959 NE Pacific Street, Box 356175 Seattle, WA 97195 E-mail: bigginss@medicine.washington.edu Tel.: 206-598-1908Search for more papers by this authorPaulo Angeli, Paulo Angeli Unit of Hepatic Emergencies and Liver Transplantation, Department of Medicine, DIMED, University of Padova, Padua, ItalySearch for more papers by this authorGuadalupe Garcia-Tsao, Guadalupe Garcia-Tsao Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT VA-CT Healthcare System, West Haven, CTSearch for more papers by this authorPere Ginès, Pere Ginès orcid.org/0000-0003-4657-4504 Liver Unit, Hospital Clinic, and Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain Centro de Investigación Biomèdica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainSearch for more papers by this authorSimon C. Ling, Simon C. Ling The Hospital for Sick Children, Division of Gastroenterology, Hepatology and Nutrition, and Department of Paediatrics, University of Toronto, Toronto, Ontario, CanadaSearch for more papers by this authorMitra K. Nadim, Mitra K. Nadim Division of Nephrology, University of Southern California, Los Angeles, CASearch for more papers by this authorFlorence Wong, Florence Wong orcid.org/0000-0001-9263-8869 Division of Gastroenterology and Hepatology, University Health Network, University of Toronto, Toronto, Ontario, CanadaSearch for more papers by this authorW. Ray Kim, W. Ray Kim orcid.org/0000-0002-3030-860X Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CASearch for more papers by this author First published: 03 May 2021 https://doi.org/10.1002/hep.31884Citations: 17 Supported by the American Association for the Study of Liver Diseases. Potential conflict of interest: Dr. Angeli advises Biovie and is on the speakers’ bureau for Grifols and Behringer. Dr. Gines received grants from Gilead, Grifols, and Mallinckrodt. Dr. Ling received grants from AbbVie and Gilead. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abbreviations AASLD American Association for the Study of Liver Diseases AKI acute kidney injury ATN acute tubular necrosis CKD chronic kidney disease HH hepatic hydrothorax HRS hepatorenal syndrome K potassium LT liver transplantation LVP large-volume paracentesis MDRO multidrug-resistant organisms MELD Model for End-Stage Liver Disease Na sodium NGAL neutrophil gelatinase-associated lipocalin NSBB nonselective beta-blocker ODS osmotic demyelination syndrome PMN polymorphonuclear PPCD postparacentesis circulatory dysfunction RA refractory ascites RRT renal replacement therapy SBE spontaneous bacterial empyema SBP spontaneous bacterial peritonitis Purpose and Scope of the Guidance This is a comprehensive guidance on the diagnosis, evaluation, and management of ascites and hepatorenal syndrome (HRS) in patients with chronic liver disease from the American Association for the Study of Liver Diseases (AASLD). It replaces the prior AASLD guideline on the same topic published in 2012 (Table 1).(1) TABLE 1. What’s New in This Guidance Because this guidance represents an update covering nearly a decade, numerous changes are made. Instead of enumerating the individual changes, the following list represents noticeable revisions: Table 3 includes specific directions on the diagnostic evaluation of ascites by clinical setting and clinical course. Tables 5 and 7 highlight specific definitions and characteristic of ascites. Figure 3 provides updated information on management of ascites, including the use of albumin in ascites. More specific definitions of hyponatremia and management are included. Updated guidance on LT for patients with HH (Table 8) and for potential candidates of simultaneous liver-kidney transplantation Table 9 has expanded and updated description of antibiotics for infections in patients with cirrhosis. The AKI section is substantially expanded and updated (Fig. 4; Tables 10-12). The pediatric section is new. This AASLD Guidance provides a data-supported approach to the management of ascites and HRS. It differs from the AASLD Guidelines, which are supported by systematic reviews of the literature, formal rating of the quality of the evidence, and strength of the recommendations. In contrast, this Guidance was developed by consensus of an expert panel and provides guidance statements based on comprehensive review and analysis of the literature on the topics, with oversight provided by the AASLD Practice Guidelines Committee. The AASLD Practice Guidelines Committee chose to perform a Guidance on this topic because a sufficient number of randomized controlled trials were not available to support meaningful systematic reviews and meta-analyses. Introduction Burden of Cirrhotic Ascites and HRS Hepatic decompensation, defined by ascites, hepatic encephalopathy, and portal hypertensive gastrointestinal bleeding, is an important landmark in the natural history of cirrhosis.(2) Ascites is commonly the first decompensation-defining event, with 5%-10% of patients with compensated cirrhosis developing ascites per year.(3) The development of ascites is associated with a reduction in 5-year survival from 80% to 30%,(4) which is due in part to patients with ascites being prone to additional complications, such as bacterial infections, electrolyte abnormalities, HRS, and nutritional imbalances, and, consequently, further clinical decline.(5) Patients with cirrhosis who develop clinically significant ascites and related complications should be considered for referral for liver transplantation (LT) evaluation and, when appropriate, palliative care.(6) HRS is a late complication of cirrhosis that accounted for 3.2% of all hospital discharges related to cirrhosis according to a 2012 study based on a large inpatient health care database of patients representative of community hospitals in the United States.(4) Moreover, the number of HRS discharges in the United States has increased significantly in the past 2 decades.(7) HRS was also associated with high inpatient mortality (~46%) as well as longer lengths of stay and higher costs of hospitalizations compared with cirrhosis discharges without HRS. Pathogenesis Figure 1 summarizes the key steps in the pathogenesis of ascites and related complications discussed in this document. From the perspective of the management of ascites, pathogenetic events of importance are renal sodium retention, arterial underfilling, and portal hypertension, which may be mitigated by diuretics, albumin infusion, and portal decompressive procedures, respectively.(8, 9) More recently, the advent of vasopressin receptor antagonists provided further insights on the contribution of water retention in the pathogenesis of ascites.(10) Recent reviews provide more detailed discussion of the pathogenesis of ascites.(11-13) FIG. 1Open in figure viewerPowerPoint Pathogenesis of ascites and related complications of cirrhosis. The central event consists of effective arterial underfilling as a result of splanchnic vasodilation leading to activation of vasoconstrictor (e.g., renin-angiotensin) and antidiuretic (e.g., arginine vasopressin) factors. Portal hypertension leading to increased sinusoidal hydrostatic pressure and increased gut permeability allowing bacterial translocation, contributing further to the pathogenesis of complications associated with ascites, including hyponatremia, AKI, HRS, and spontaneous bacterial infections. Abbreviation: AQP21, Aquaporin-2. HRS is a functional renal failure resulting from hemodynamic changes occurring in patients with ascites and portal hypertension.(14) The primary pathophysiologic mechanism of HRS is reduced renal perfusion secondary to renal vasoconstriction mediated by increased activities of the sympathetic, renin-angiotensin-aldosterone, and vasopressin systems,(5) which may be further aggravated by decreased cardiac output in patients with cirrhosis-associated cardiomyopathy. In addition, systemic inflammation that is common among patients with decompensated cirrhosis may trigger immune-mediated renal injury.(15) Finally, emerging evidence suggests that renal autoregulation, a natural defense mechanism to maintain renal blood flow, is impaired in patients with cirrhosis, predisposing them to additional direct hemodynamic renal injury.(16) Together, structural kidney damage can follow severe and/or repeated episodes of such renal events.(17, 18) Initial Diagnosis and Management of Ascites Diagnostic Evaluation of a Patient With Ascites Although cirrhosis is the most common cause of ascites in the Western world, other potential causes should be considered, including malignancy, heart failure, tuberculosis, and pancreatic disease. The initial evaluation of ascites should include history, physical examination, abdominal doppler ultrasound, laboratory assessment of liver and renal function, serum and urine electrolytes, and a diagnostic paracentesis for analysis of the ascitic fluid (Fig. 2; Tables 2-4).(19, 20) In evaluating the etiology of ascites, the serum albumin ascites gradient is calculated by subtracting the ascitic fluid albumin from the serum albumin in simultaneously obtained samples.(21) A serum albumin ascites gradient ≥1.1 g/dL is highly suggestive of portal hypertension, usually caused by liver disease with an accuracy of approximately 97%, whereas a serum albumin ascites gradient <1.1 g/dL suggests other causes of ascites (Table 4). In contrast, a high ascitic fluid protein (>2.5 g/dL) supports a cardiac source for ascites.(22) Other tests of the ascitic fluid, such as amylase, cytology, or culture for mycobacteria, are not routinely indicated but should be guided by the patient’s clinical context. FIG. 2Open in figure viewerPowerPoint Diagnostic approach to new-onset ascites. 1May include right heart catheterization. Abbreviations: Abd, abdominal; ADA, adenosine deaminase; AFB, acid fast bacterium; HV, hepatic venous; SAAG, serum-ascites albumin gradient; TJLB, transjugular liver biopsy. TABLE 2. Initial Evaluation of Patients With Ascites Medical history: Risk factors for chronic liver disease (alcohol, metabolic, viral hepatitis, family history of liver disease), heart disease, hematologic disorder (thrombosis, excessive bleeding), thyroid disease, autoimmune disorder, malignancy, pancreatitis, travel history, and risk factors for tuberculous Physical examination: Shifting abdominal dullness, abdominal masses or tenderness or guarding, umbilical/inguinal hernias, evidence of HH (decreased breath sounds or thoracic dullness to percussion), stigmata of chronic liver disease (splenomegaly, spider angioma, palmar erythema, or abdominal wall collaterals), signs of heart failure or constrictive pericarditis (jugular venous distension, pulmonary congestion, pericardial rub), signs of malignancy or infection (lymphadenopathy), signs of malnutrition (sarcopenia), signs of thyroid disease Abdominal ultrasonography with Doppler Complete blood count Liver function tests (INR, serum total bilirubin, serum albumin) Renal function tests (serum creatinine, BUN) Serum and urine electrolytes (Na, K) and urine analysis with spot urine protein Ascitic fluid analysis (see Table 3 and Fig. 2): SAAG, total protein concentration, polymorphonuclear leukocyte count, and culture Abbreviations: BUN, blood urea nitrogen; INR, international normalized ratio; SAAG, serum albumin ascites gradient. TABLE 3. Guidance to Diagnostic Paracentesis in Patients With Cirrhosis What to Test First Episode of Ascites Recurrent Ascites Inpatients Outpatients Inpatients Outpatients** Including those admitted to one day hospital for LVP. SAAG Yes Yes No No PMN count Yes Yes Yes Yes Culture Yes No Yes No Protein concentration Yes Yes Only when a primary prophylaxis of SBP is clinically indicated or a secondary bacterial peritonitis is suspected Only when a primary prophylaxis of SBP is clinically indicated Glucose concentration Only when a secondary bacterial peritonitis is suspected No Only when a secondary bacterial peritonitis is suspected No Lactate dehydrogenase Only when a secondary bacterial peritonitis is suspected No Only when a secondary bacterial peritonitis is suspected No Cytology Only when causes of ascites other than cirrhosis are suspected Only when causes of ascites other than cirrhosis are suspected No No Amylase concentration Only when a pancreatic origin of ascites is suspected Only when a pancreatic origin of ascites is suspected No No * Including those admitted to one day hospital for LVP. Abbreviation: SAAG, serum albumin ascites gradient. TABLE 4. Interpretation of SAAG in Discriminating the Cause of Ascites SAAG ≥ 1.1 g/dL Reflects Portal Hypertension SAAG < 1.1 g/dL Excludes Portal Hypertension Potential cause of ascites Potential cause of ascites Ascites in cirrhosis Peritoneal carcinomatosis Ascites related to massive liver metastasis Tuberculosis peritonitis Ascites related to liver involvement in right heart failure Other clinical conditions Abbreviation: SAAG, serum albumin ascites gradient. In patients with cirrhosis, ascites can be graded according to the amount of fluid accumulated in the abdominal cavity and classified according to response to treatment (Table 5).(19) No treatment is recommended for grade 1 ascites, as there is no evidence that it improves patient outcomes. Response to therapy and subsequent outcome in patients with grade 2 or 3 ascites depends on several factors such as the underlying cause of cirrhosis; feasibility and effectiveness of therapy to alter the natural course of cirrhosis; presence of superimposed complications such as renal failure, hyponatremia, and spontaneous bacterial peritonitis (SBP); and adherence of the patient to dietary sodium restriction and diuretics. TABLE 5. Classification of Ascites According to Amount of Fluid Accumulation According to the Response to Treatment Grade 1. Mild ascites Only detected by ultrasound Responsive ascites Ascites that can be fully mobilized or limited to grade 1 with diuretic therapy associated or not to moderate dietary sodium restriction Grade 2. Moderate ascites Moderate symmetric distension of abdomen Recurrent ascites Ascites that recurs on at least 3 occasions within a 12-month period despite dietary sodium restriction and adequate diuretic dosage Grade 3. Large or gross ascites Marked distension of the abdomen Refractory Ascites Ascites that cannot be mobilized or the early recurrence of which (i.e., after LVP) cannot be satisfactorily prevented by medical therapy Guidance Statements A diagnostic paracentesis should be performed in all patients with new-onset ascites that is accessible for sampling. The initial laboratory investigation of ascitic fluid should include ascitic fluid neutrophil count, ascitic fluid total protein, ascitic fluid albumin, and serum albumin to calculate the serum-ascites albumin gradient. Dietary Sodium Restriction and Diuretic Therapy Moderate dietary sodium restriction (2 g or 90 mmol/day) should be prescribed to achieve a negative sodium balance and net fluid loss. Fluid restriction is not indicated unless hyponatremia is present. Patient education for sodium restriction is essential to maximize adherence while avoiding malnutrition and sarcopenia.(23-25) Instructions about a sodium-restricted diet should include advice on sodium contents of preprepared meals, avoiding adding salt to cooked meals, and guarding against nutritional deficiency.(23) A formal consultation with a dietician should be considered. In most patients with cirrhosis presenting with ascites, dietary sodium restriction alone is insufficient and diuretic therapy is necessary. The patient should be made aware that daily monitoring of body weight, preferably at the same time of the day, is essential in assessing the efficacy of diuretics and preventing their adverse effects. The peritoneal membrane’s ability to reabsorb ascites from the abdominal cavity is limited to approximately 500 mL per day. Thus, in a patient without peripheral edema, weight loss exceeding 0.5 kg per day may result in plasma volume contraction, predisposing the patient to renal failure and hyponatremia. In those with edema, weight loss up to 1 kg/day may be tolerated.(19, 26) In addition, patients should understand the need for laboratory monitoring (e.g., serum electrolyte concentrations), particularly during the first weeks of treatment. Assessment of 24-hour urinary sodium excretion may be useful to guide therapy; in the absence of renal dysfunction, sodium excretion lower than the intake (e.g., 80 mmol/day) indicates an insufficient diuretic dose. Persistent ascites despite adequate urinary sodium excretion indicates dietary indiscretion. When a 24-hour urine collection is not feasible, a random “spot” urine sodium concentration that is greater than the potassium (K) concentration correlates well with 24-hour urine sodium excretion.(27, 28) When the spot urine sodium (Na)/K ratio is >1, the patient should be losing fluid weight,(28) and, if not, dietary noncompliance should be suspected. If the spot urine Na/K ratio is ≤1, there is insufficient natriuresis, and an increase in diuretics should be considered. Aldosterone antagonists (e.g., spironolactone) and loop diuretics (e.g., furosemide, torsemide, bumetanide) are the mainstay of diuretic treatment of cirrhotic ascites.(29, 30) Two studies addressing the best way to use these diuretics showed that for the first episode of ascites, treatment with aldosterone antagonists alone generated an adequate response with few side effects,(29, 30) whereas those with long-standing ascites responded better to a combined diuretic treatment.(31) The recommended initial dose of spironolactone is 100 mg/day, which can be progressively increased up to 400 mg/day. Spironolactone and its active metabolites have a long half-life; the full effect of a dose change may not be seen for up to 3 days. When the dose is increased, it should be done cautiously and in a stepwise fashion, with an interval of at least 72 hours. The dose of furosemide (initially 40 mg/day) may be progressively increased, according to the response and tolerability toward 160 mg/day, which is the generally accepted threshold to determine medical treatment refractoriness.(19, 26) Torsemide or bumetanide may improve natriuresis in patients with a suboptimal response to furosemide.(32) Patients with chronic kidney disease (CKD) in general are treated with higher doses of loop diuretics and lower doses of aldosterone antagonists. When ascites is adequately mobilized, attempts should be made to taper the diuretics to the lowest dosages to maintain minimal or no ascites. Adverse effects of diuretic therapy may occur in 20% and 40% of patients with cirrhosis and ascites (Table 6).(23) Painful gynecomastia can be caused or exacerbated by spironolactone, which may respond to switching to amiloride or eplerenone(33, 34); see Table 6 for conversion doses. Muscle cramps are common in patients with liver disease, particularly in patients on diuretic treatment for ascites, and adversely influence the quality of life.(35) The exact mechanisms by which they occur remain unclear; however, besides the correction of electrolyte alterations (e.g., hypokalemia and hypomagnesemia), muscle cramps may respond to medications, such as baclofen (10 mg/day, with a weekly increase of 10 mg/day up to 30 mg/day)(36) and albumin (20-40 g/week).(35) Other drugs such as orphenadrine(37) and methocarbamol(38) have been proposed for muscle cramps in patients with cirrhosis. Finally, quinidine at a dose of 400 mg/day for 4 weeks in patients with cirrhosis was more effective than placebo against painful muscle cramps; however, toxicities such as diarrhea in about one-third of cases requiring treatment withdrawal may limit its use.(39) TABLE 6. Adverse Effects of Diuretic Agents AKI (rise of at least 0.3 mg/dL in 48 hours): mostly related to loop diuretics, as these patients are highly vulnerable to rapid reduction of extracellular fluid volume due to their hemodynamic status Hyponatremia (<135 mmol/min): more common with loop diuretics, as they inhibit Na-K-Cl transporter and, therefore, solute-free water generation Hypokalemia (serum potassium <3.5 mmol/L): more common with loop diuretics Hyperkalemia (serum potassium >5.5 mmol/L): more common with aldosterone antagonists, especially if concomitant impaired renal perfusion; also with use of angiotensin-converting enzyme inhibitors Hepatic encephalopathy: more common with other diuretic-induced side effects (i.e., hyponatremia, reduction of extracellular volume) Gynecomastia: often painful, more common with aldosterone antagonist; more common with spironolactone than with eplerenone or amiloride** Suggested conversion of spironolactone of 100 mg, ~50 mg of eplerenone, ~10 mg of amiloride. Muscle cramps: can lead to impairment of quality of life and mobility * Suggested conversion of spironolactone of 100 mg, ~50 mg of eplerenone, ~10 mg of amiloride. Abbreviations: Cl, chlorine; Na-K-Cl, sodium-potassium-chloride. Treatment of Grade 3 Ascites For patients presenting with tense ascites, large-volume paracentesis (LVP) combined with hyperoncotic human albumin is the initial treatment of choice, even in the presence of hyponatremia.(40, 41) Patients with massive peripheral edema may require a second paracentesis shortly after the first because a rapid shift of fluid may occur from interstitial tissue to the abdominal cavity.(19, 26, 40, 42) After LVP and a significant reduction in the intra-abdominal pressure, diuretics can be instituted, which may eliminate or reduce the frequency of paracentesis.(43) More detailed discussion about LVP is found in the section on refractory ascites (RA). Guidance Statements Moderate sodium restriction (2 g or 90 mmol/day) and diuretics (spironolactone with or without furosemide) are the first-line treatment in patients with cirrhosis and grade 2 ascites. After ascites is adequately mobilized, attempts should be made to taper the diuretics to the lowest dose necessary to maintain minimal or no ascites to prevent the development of adverse effects. Fluid restriction is not necessary for ascites management unless there is concomitant moderate or severe hyponatremia (serum sodium ≤ 125 mmol/L). In patients receiving diuretics, body weight and serum creatinine and sodium should be regularly monitored to assess response and to detect the development of adverse effects. Human albumin solution (20-40 g/week) or baclofen administration (10 mg/day, with a weekly increase of 10 mg/day, up to 30 mg/day) can be considered in cases of severe muscle cramps. LVP is the first-line treatment of grade 3 ascites. After paracentesis, sodium restriction and diuretics should be started. Referral for LT evaluation should be considered in patients with grade 2 or 3 ascites. General Medical Management of Patients With Cirrhosis and Ascites Given the hemodynamic abnormalities in patients with cirrhosis and ascites, medications that may further reduce effective arterial volume and renal perfusion should be avoided. The most commonly encountered example is nonsteroidal anti-inflammatory drugs, which may precipitate hyponatremia, diuretic refractoriness, and acute kidney injury (AKI).(44) The angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, α1-adrenergic blockers, and dipyridamole should also be avoided.(45-48) Similarly, all potential nephrotoxins should be avoided in patients with cirrhosis and ascites. Aminoglycoside antibiotics should be avoided whenever possible in the treatment of bacterial infections.(49) Finally, in patients with cirrhosis and ascites, the use of IV contrast media is not contraindicated(50); however, caution needs to be exercised in patients with impaired renal function. Albumin, the most abundant serum protein, is the main component that generates the oncotic pressure. In addition, albumin has a multitude of other functions, including ligand binding, anti-inflammatory, antioxidant, and endothelial stabilizing effects.(51-53) Recently, long-term albumin administration to patients with decompensated cirrhosis has been studied.(54, 55) In the ANSWER study, 431 patients with diuretic-responsive ascites were randomized to either standard medical treatment or standard medical treatment plus 40 g of albumin twice a week for the initial 2 weeks and then 40 g once a week for 18 months. A significantly better overall survival was seen in patients receiving albumin, with a 38% reduction in mortality.(54) In the MACTH study, 173 patients with ascites listed for LT were randomized to receive standard medical treatment plus 40 g of albumin every 15 days and an α1-receptor agonist, midodrine (15-30 mg/day depending on the response), or standard medical treatment plus placebo. Despite some improvement in parameters reflecting improved effective plasma volume, no difference was observed in the complication rates or death during 12 months of follow-up.(55) Thus, the discrepant results between the two trials point to the need for further studies to address the role of albumin as well as cost-effectiveness(56) in the management of ascites. Given the complexity of medical care of patients with cirrhosis and ascites, the use of a multidisciplinary team is likely beneficial but has not been studied extensively. A model of specialized care has been proposed: an integrated team including hepatologists, dedicated nurses, physicians in training, and diagnostic facilities improved 12-month survival and reduced the rate of hospitalization for liver-related complications in o