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

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) 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: 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. 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. 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) 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) 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. 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. 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) 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). 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 outpatients with cirrhosis and ascites compared with standard practice.(57) RA occurs in approximately 5%-10% of all patients with cirrhosis and ascites and is associated with poor survival of 50% at 6 months.(58) RA is defined as ascites that cannot be mobilized or recurs after LVP despite dietary sodium restriction and diuretic therapy.(19) Thus, RA is further divided into (1) diuretic resistant (i.e., persistent ascites despite maximal doses of diuretics) and (2) diuretic intractable, in which side effects of diuretics preclude the use of maximum doses (Table 7).(59) Recurrent ascites, which is defined as ascites that recurs at least three times within 1 year despite dietary sodium restriction and diuretic therapy, may be a forerunner of RA.(59) Figure 3 outlines the suggested treatment algorithm for RA management. Diuretic-resistant ascites Because of the lack of response to dietary sodium restriction and maximal doses of diuretics Diuretic-intractable ascites Because of the development of diuretic-induced complications* that precludes the use of effective doses of diuretics Fails sodium restriction Fails maximum doses of diuretics Both for at least 1 week Lack of treatment response Early recurrence of ascites *Diuretic-induced complications Dietary sodium restriction is important in the management of patients at all stages of ascites, including those with recurrent or refractory ascites, as it lowers the rate of ascites accumulation. Frequent review of a food diary can help identify high-sodium food items if the patient is reaccumulating ascites rapidly. Some patients who have been labeled as having RA may reduce their ascites once they adhere to a low-sodium diet. This is especially true in patients who excrete approximately 80 mmol of sodium in their urine per day.(28) Fluid restriction in a patient with cirrhosis and RA is difficult to enforce and is often impractical. These patients' daily urine output is usually less than 1 L, making it virtually impossible to achieve a negative fluid balance by restricting fluid intake to less than the urine output. The serum sodium concentration at which fluid restriction should be instituted has not been well defined(60) but is recommended when serum sodium is ≤125 mmol/L or its onset is rapid (see the section on hyponatremia). In patients who have diuretic-resistant ascites, the continued use of diuretics is ineffective while predisposing patients to complications, especially renal impairment. Furthermore, loop diuretics have a sigmoidal dose-response curve, which means that once the ceiling dose is reached, further increase in doses will not increase renal sodium excretion. For patients with liver cirrhosis, this ceiling dose is reduced compared with healthy controls.(61) In patients with diuretic intractable ascites, there are no data as to whether diuretic doses lower than those that have produced side effects should be used once the side effects have abated. Chronic albumin infusion in patients with cirrhosis and RA was evaluated in a cohort of 70 participants, 45 of whom received 20 g of albumin twice weekly.(62) There was a significant reduction in the 24-month hospital admissions for complications of cirrhosis and mortality.(62) These results suggest that the use of albumin is generally safe and may be beneficial in patients with RA, but randomized controlled trials are needed to support these findings. The dose of albumin used may be critical in achieving positive results.(63) LVP, arbitrarily defined as a paracentesis of >5 L, has been shown to be safe and effective in the management of RA. When done repeatedly, LVP has a lower incidence of electrolyte abnormalities, renal dysfunction, and hemodynamic disturbance with similar survival compared with continued diuretic use.(40) In patients undergoing LVP, the use of albumin is crucial to prevent a further reduction of effective arterial blood volume, which may precipitate postparacentesis circulatory dysfunction (PPCD). The clinical manifestations of PPCD include renal impairment, including HRS, dilutional hyponatremia, hepatic encephalopathy, and death.(64, 65) Albumin infusion is particularly important if more than 5 L of ascites are removed to prevent the development of PPCD.(28, 66) Paracenteses of a smaller volume are not associated with significant hemodynamic changes,(67) and albumin infusion may not be required. Although there has not been a dose-response study on albumin use with LVP, the administration of 6-8 g of albumin per liter of ascites removed has been recommended.(19) For example, after the fifth liter, approximately 40 g of albumin should be infused, and after 8 L removal, the amount of albumin given should be approximately 64 g. It has been held that there is no limit for the amount of ascites that can be removed in a single session, provided an appropriate amount of albumin is administered. However, the risk of PPCD increases with >8 L of fluid evacuated in one single session. A recent study showed that by limiting the LVP volume to <8 L per session and providing a higher than recommended dose of albumin (9.0 ± 2.5 g per liter of ascites removed), renal function and survival may be better preserved over a mean period of 2 years despite the development of PPCD in 40% of patients.(68) In patients with hemodynamic instability (systolic blood pressure <90 mm Hg), hyponatremia (serum sodium <130 mmol/L), and/or the presence of AKI, albumin infusion should be strongly considered for paracentesis of a smaller volume.(69) LVP is a safe procedure even in the presence of coagulopathy. In a study that included patients with an international normalized ratio of >1.5 and a platelet count of <50 × 109/L, only 1% of patients experienced minimal cutaneous bleeding after LVP.(70) Therefore, elevated prothrombin time or thrombocytopenia is not a contraindication for paracentesis, nor is transfusion of clotting factors or platelets recommended. Possible exceptions may include patients with disseminated intravascular coagulation or uremia and thrombocytopenia. In the latter patients, desmopressin may be considered, particularly if there is history of prior bleeding.(71) Given its ability to reduce the portal pressure effectively, TIPS in well-selected patients with RA has been shown to be better than repeated LVP in the control of ascites.(72, 73) Survival advantage with TIPS insertion in patients with RA is reported in recent studies, including a meta-analysis.(74-76) This may be especially true for younger patients with low Model for End-Stage Liver Disease (MELD) scores, those who received a smaller diameter covered stent, and those who had a complete response to TIPS with total elimination of ascites.(77-80) Physiologically, reduction of portal pressure with TIPS insertion allows gradual return of the splanchnic volume to the systemic circulation through the TIPS, thereby improving the effective blood volume. In turn, there is gradual suppression of the activated neurohormonal vasoconstrictor systems over 4-6 months, at which time, a significant diuresis occurs with elimination of ascites.(81) Therefore, it is important to manage patients' expectations that the clearance of ascites is not immediate post-TIPS, and patients should be maintained on a sodium-restricted diet until ascites is adequately controlled. Caution is recommended about the use of diuretics post-TIPS, as diuretics reduce the intravascular volume, which may slow the refilling of the effective arterial blood volume and counteract the volume refilling effects of TIPS insertion, potentially delaying ascites clearance. Eventually, approximately 80% of patients will clear their ascites with TIPS.(77) Patients who fail to do so despite a widely patent TIPS at 12 months should be referred for LT evaluation. Complications of TIPS may be related to the insertion procedure, the TIPS prosthesis, or the presence of a shunt, which are discussed in detail in the AASLD guidance on the topic.(82) In patients with RA undergoing TIPS, TIPS prostheses covered with polytetrafluoroethylene have lessened the incidence of TIPS dysfunction significantly.(83) The utility of Doppler ultrasound in the management of TIPS depends on the setting.(84) Confirmation of the function soon after the stent placement is helpful. Follow-up interrogation of the stent in asymptomatic patients with a covered stent probably has little therapeutic impact; however, long-term surveillance has been suggested in patients who received revisions for TIPS dysfunction and in patients with a prothrombotic state.(85) Conversely, as Doppler studies may miss TIPS stenosis, venography should be considered in patients with persistent or recurrent ascites even if the Doppler is reportedly unremarkable. Patient selection and timing for TIPS is of critical importance for a successful outcome. In general, patients with high MELD scores of ≥18 are poor candidates to receive a TIPS.(79) Certain risk factors (e.g., advanced age, cardiopulmonary insufficiency, and sarcopenia) predispose patients to more complications post-TIPS and hepatic encephalopathy,(86-88) although sarcopenia per se may not affect survival after TIPS insertion for RA.(89) TIPS stents with a smaller (8-10 mm) diameter than conventional ones have been associated with lower incidence of post-TIPS hepatic encephalopathy without compromising the efficacy on ascites control.(90-92) A recent study suggests that TIPS inserted at an earlier stage of ascites' natural history (such as those with recurrent ascites) could result in fewer side effects and improved survival when compared with LVP.(93) The 1-year transplant-free survival of 93% was significantly better than 53% in patients who received repeat LVP, albumin, and diuretics. There was also no difference in the incidence of hepatic encephalopathy during follow-up. However, this concept of early TIPS insertion will need to be replicated in a randomized controlled trial before it can be recommended. For patients who are not TIPS candidates, the safety and efficacy of permanent indwelling peritoneal catheters remain to be established.(94) The studies published so far are of low quality, in which the average bacterial infection rate was 13%.(81) The risk and benefit ratios are even less certain for Child C patients, for whom repeat LVP remains a treatment option. The automatic low flow ascites pump (alfapump; Sequana Medical NV; Ghent, Belgium) is an implantable battery-powered pump that transports ascites from the peritoneal cavity into the bladder, allowing the elimination of ascites by urination. Insertion of an alfapump was reported to reduce paracentesis requirement, together with improvement in quality of life and nutritional status.(95) Currently, the alfapump is not available in North America. Patients who have RA and concomitant significant liver dysfunction that precludes TIPS placement should be considered for LT. Patients who have RA but preserved liver function may be disadvantaged under the current MELD-based organ allocation system, as patients with ascites may bear an additional mortality risk equivalent to 4.5 MELD points,(96) especially in patients whose MELD score is <21.(97) Many patients with RA also have hyponatremia, which is addressed by the MELD-sodium score.(98-101) Following LT, the hemodynamic abnormalities of decompensated cirrhosis will take weeks to months to correct. Patients may continue to have ascites for some time in the posttransplant period and will need to stay on a sodium-restricted diet until clearance of ascites. Nonselective beta-blockers (NSBBs) are the standard of care for the prevention of variceal bleeding in patients with cirrhosis and portal hypertension. More recently, the use of NSBB was found to be associated with a higher likelihood of PPCD(102) and shorter survival in decompensated cirrhosis, including patients with RA(103, 104) and SBP.(105) Other publications soon followed that showed no impact of NSBB use on AKI development(106) or on mortality,(107, 108) even in patients with severe liver dysfunction and those with acute-on-chronic liver failure.(109) These seemingly contradictory results led to the proposal of the "window period" hypothesis, suggesting that NSBBs were only useful during a certain window of period in the natural history of cirrhosis.(110) Beyond that time, NSBB use could be detrimental. It is important to note that none of the studies quoted so far are randomized controlled trials. In the only randomized controlled trial conducted in patients with compensated cirrhosis, the use of NSBB was associated with a reduced incidence of ascites, suggesting that the use of NSBB in the early stage of cirrhosis is beneficial.(111) To resolve the controversy, adequately powered, randomized controlled studies using hard end points such as survival are needed in patients with decompensated cirrhosis. For now, we can only caution the use of NSBB in patients with RA, especially in those with hemodynamic abnormalities as indicated by low systolic blood pressure <90 mm Hg, hyponatremia with serum sodium <130 mmol/L, or serum creatinine of >1.5 mg/dL.(112) NSBBs might be reintroduced if circulatory dysfunction improves with improvement of these parameters. Hyponatremia, defined as a serum Na concentration ≤135 mEq/L, is present in nearly half (49%) of patients with cirrhosis and ascites, with over a fifth (22%) having serum Na levels ≤130 mEq/L.(113) Most patients with cirrhosis, ascites, and hyponatremia have hypervolemic hyponatremia; however, hypovolemic and euvolemic hyponatremia should be considered. Hypovolemic hyponatremia can occur because of poor oral intake or from urinary or gastrointestinal losses related to an excess of diuretic or laxative treatments, respectively. Euvolemic hyponatremia is uncommon among patients with cirrhosis unless there is a specific cause, such as syndrome of inappropriate antidiuretic hormone secretion, medications (e.g., sertraline, carbamazepine), and severe hypothyroidism or adrenal insufficiency. Symptoms of hyponatremia, although infrequent in patients with cirrhosis, range from nausea, muscle cramps, gait instability, lethargy, headache, and dizziness to confusion and seizure. Improvement in hyponatremia is associated with reduced brain edema and improved cognition, quality of life,(114) and complex information processing.(115) The severity of hyponatremia with cirrhosis is graded as mild (126-135 mEq/L), moderate (120-125 mEq/L), and severe (<120 mEq/L). Mild hyponatremia often does not require specific management apart from monitoring and water restriction; however, patients with symptomatic hyponatremia, moderate or severe hyponatremia, and imminent LT may require specific management. Hyponatremia reflects worsening of hemodynamic status as cirrhosis advances (Fig. 1). Patients with cirrhosis and serum Na ≤130 mEq/L are at increased risk for developing hepatic encephalopathy (odds ratio, 3.4), HRS (odds ratio, 3.5), and SBP (odds ratio, 2.4),(113) and they have a higher in-hospital(86) and waitlist mortality.(98, 100, 101) Even patients with modest hyponatremia (serum Na 131-135 mEq/L) may be at increased risk of these serious complications.(113) This finding prompted the inclusion of serum Na into the liver allocation system in the United States in 2016, giving access to LT for patients with hyponatremia.(99) Treatment of hyponatremia in cirrhotic ascites depends on etiology, ch