Keywords

FormalPara Key Concepts

  • Ascites is the most common complication of cirrhosis. It is associated with a high risk of further complications such as dilutional hyponatremia, spontaneous bacterial peritonitis (SBP), refractory ascites and hepatorenal syndrome (HRS)

  • Diuretics are the mainstay of treatment for uncomplicated ascites. However, the development of any complication requires a specific approach which can consist of drug implementation (e.g. antibiotics for SBP, terlipressin and albumin for acute and rapidly progressive HRS) and, in patients with refractory ascites, can consider transjugular intrahepatic porto-systemic shunt (TIPS) allocation.

  • Liver transplantation represents the best treatment of patients with complicated ascites which is a clinical hallmark of poor survival. In several countries refractory ascites is considered an exception to the MELD score in the allocation of priority in patients with cirrhosis on the waiting list

1 Introduction

Ascites is the most common of the three major complications related with cirrhosis, being the others hepatic encephalopathy and variceal hemorrhage [1]. Ascites is associated with a high incidence of further complications of cirrhosis. In fact, patients with ascites have a high risk of developing dilutional hyponatremia, bacterial infections, in particular spontaneous bacterial peritonitis (SBP), and a specific type of acute kidney injury (AKI), namely hepatorenal syndrome (HRS) [1].

2 Classification and Management of Ascites

Ascites can be classified into complicated and uncomplicated ascites. Complicated ascites is defined in association with at least one among hyponatremia, refractoriness to diuretic treatment, acute kidney injury and SBP [1]. In addition, ascites can be quantified in three grades according to its amount in the peritoneal cavity: (1) mild ascites only detectable by ultrasound; (2) moderate ascites with symmetrical distension of the abdomen; (3) large ascites. The first step in the management of ascites is to collect a detailed medical history and to perform liver and renal blood tests and an abdominal ultrasound. A paracentesis should be performed in all patients with first onset of grade 2/3 ascites and/or acutely decompensated. Peritoneal fluid analysis can provide relevant information such as the confirmation of ascites as a consequence of portal hypertension [serum albumin ascites gradient (SAAG) ≥1.1 g/dl], the presence/absence of an SBP (neutrophil cell count [250 cells/μl]) and the risk of developing SBP during follow-up (total protein content <1.5 g/dl) [1]. Before discussing the specific treatment of ascites, it should be highlighted that an important issue in the management of patients with cirrhosis is the treatment of the underlying cause of liver disease. In fact, several data suggest that the antiviral treatment of HBV and HCV and/or alcohol abstinence may lead to a progressive improvement of liver function with the potential prevention of the first episode of ascites in patients with compensated cirrhosis and the potential improvement of the response to diuretics in already decompensated patients.

2.1 Uncomplicated Ascites

The treatment of uncomplicated ascites should be adapted to the ascites grade. The clinical impact of grade 1 ascites have not been extensively investigated and no specific treatment has been suggested. The aim of treatment of moderate ascites is to induce a negative sodium balance with a moderate restriction in salt intake and diuretic use to increase renal sodium excretion.

2.1.1 Sodium Intake Restriction

Although there is no clear evidence of the efficacy of low sodium intake in the management of ascites in cirrhosis, the current guidelines suggest a moderate restriction of dietary salt (80–120 mmol of sodium/day, equivalent to approximately 4.6–6.9 g of salt/day) [1]. A lower sodium intake is often intolerable to patients, and also might worsen the malnutrition frequently observed in these patients [2].

2.1.2 Diuretics

Renal sodium retention in patients with ascites due to cirrhosis is mainly due to increased proximal as well as distal tubular sodium reabsorption [3]. The mediators of the enhanced proximal tubular reabsorption of sodium have not been elucidated completely, while aldosterone stimulates renal sodium reabsorption along the distal tubule by increasing both the permeability of the luminal membrane of principal cells to sodium and the activity of the Na/K ATPase pump in the basolateral membrane, therefore, aldosterone antagonists, such as spironolactone are used for first-line diuretics to treat ascites [3]. Aldosterone antagonists should be administered starting from 100 to 200 mg/day. A stepwise increase of aldosterone antagonist doses (up to 400 mg/day) may be effective in mobilizing ascites in 60–80% of nonazotemic cirrhotic patients with a first episode of ascites [1]. A long-standing debate in the management of ascites is whether aldosterone antagonists should be given alone or in combination with a loop diuretic (i.e., furosemide). Since the effect of aldosterone is slow, as it involves interaction with a cytosolic receptor and then a nuclear receptor, a sequential increase of antialdosteronic drugs requires a long time to find the effective dose, especially for patients with recurrent ascites [3]. A combined diuretic treatment has been proposed with the administration of a low dose of furosemide (up to 160 mg/day) and 100–400 mg/day of an antialdosteronic drug [3].

Amiloride can be substituted for spironolactone in patients with tender gynecomastia. However, amiloride is more expensive and has been shown to be less effective than an active metabolite of spironolactone [1]. Triamterene, metolazone, and hydrochlorothiazide have also been used for ascites [1]. Hydrochlorothiazide can also cause rapid development of hyponatremia when added to the combination of spironolactone and furosemide; it should be used with extreme caution or avoided [1]. In all patients, diuretic dosage should be adjusted to achieve a rate of weight loss of no greater than 0.5 kg/day in patients without peripheral edema and 1 kg/day in those with peripheral edema to prevent diuretic-induced renal failure and/or hyponatremia [1]. Following mobilization of ascites, diuretics should be reduced to maintain patients with minimal or no ascites to avoid diuretic-induced complications.

2.1.3 Complications of Diuretic Therapy

The use of diuretics may be associated with several complications such as renal failure, hepatic encephalopathy, electrolyte disorders, gynecomastia, and muscle cramps [1, 4]. Diuretic-induced renal failure is most frequently due to intravascular volume depletion that usually occurs as a result of an excessive diuretic therapy [1, 4]. Diuretic therapy has been classically considered a precipitating factor of hepatic encephalopathy. Hypokalemia may occur if patients are treated with loop diuretics alone. Hyperkalemia may develop as a result of treatment with aldosterone antagonists or other potassium-sparing diuretics, particularly in patients with renal impairment. Hyponatremia is another frequent complication of diuretic therapy, most experts agree that diuretics should be stopped temporarily in patients whose serum sodium decreases to less than 120–125 mmol/L. Gynecomastia is common with the use of aldosterone antagonists, but it does not usually require discontinuation of treatment. Finally, diuretics may cause muscle cramps [1, 4]. If cramps are severe, diuretic dose should be decreased or stopped and albumin infusion may relieve symptoms [1, 4].

2.2 Large Ascites

In patients with large ascites the first-line treatment should be the combination of large volume paracentesis (LVP) and infusion of albumin because is more effective than diuretics and significantly shortens the duration of hospital stay [1, 3]. In addition, the frequency of hyponatremia, renal impairment, and hepatic encephalopathy is significantly lower with paracentesis than with diuretic treatment. Hemorrhagic complications after LVP are infrequent even in patients with INR >1.5 and platelet count <50,000/μl [5]. Thus, there are no data to support a systematic use of fresh frozen plasma or pooled platelets before LVP.

The mobilization of ascites can be completed in one single tap. The removal of large volumes of ascitic fluid is associated with circulatory dysfunction characterized by a ≥50% increase of plasma renin activity 1 week after the procedure [6], a reduction of effective blood volume, an acute increase of cardiac output and a reduction in the systemic vascular resistance and arterial blood pressure, a condition known as post-paracentesis circulatory dysfunction (PPCD) [6]. PPCD is a relevant complication, being associated with a rapid recurrence of ascites, a high incidence of HRS, dilutional hyponatremia and death [6]. The most effective method to prevent circulatory dysfunction after LVP is plasma volume expansion. Albumin, at the dose of 8 g/l of ascites removed, is more effective than other plasma expanders for the prevention of PPCD [7] and to reduce the mortality rate in patients with ascites [7]. When less than 5 L of ascites are removed, dextran-70 (8 g/L of ascites removed) or polygeline (150 ml/L of ascites removed) show efficacy similar to that of albumin. However, albumin should be preferred because it is more effective [8]. Patients treated with LVP should immediately receive diuretic treatment after the removal of ascitic fluid to prevent the re-accumulation of ascites [4].

2.3 Refractory Ascites

Refractory ascites is defined as “ascites that cannot be mobilized or the early recurrence of which (i.e. after paracentesis) cannot be satisfactorily prevented by sodium restriction and diuretic treatment” [3]. Two different types of RA have been described: diuretic-resistant ascites [that do not respond to dietary sodium restriction and maximal diuretic dose (furosemide 160 mg/day and aldosterone antagonists 400 mg/day)] and diuretic-intractable ascites (caused by the development of diuretic-related complications) [3]. The latter accounts for more than 90% of patients with refractory ascites [3]. Refractory ascites occurs in 5–10% of patients with cirrhosis and ascites and is associated with a low probability of survival, about 50% at 6 months [3]. The treatment includes LVP with albumin, liver transplantation (LT), vasoconstrictors or insertion of a transjugular intrahepatic portosystemic shunt (TIPS). The use of therapies under investigation will also be discussed briefly.

2.3.1 Liver Transplantation (LT)

LT represents the best treatment of patients with refractory ascites who have a poor survival, even worse than that predicted by the MELD score. Thus, in several countries refractory ascites is considered an exception to the MELD score and indicates priority for transplantation in waiting list patients [8]. However, many patients with refractory ascites have contraindications to LT. These patients need some other therapeutic options. The same happens for the management of patients with large ascites while on waiting list.

2.3.2 Vasoconstrictors

Vasoconstrictors, such as the α1-adrenergic agonist midodrine or the vasopressin-1 (V1) receptor agonist terlipressin may decrease the splanchnic arterial vasodilatation and thereby improve the renal perfusion and filtration [9, 10]. In patients with ascites, a single oral dose of midodrine increases the arterial blood pressure, renal perfusion, glomerular filtration rate (GFR) and sodium excretion but this drug is not recommended as standard of therapy [9]. The administration of terlipressin has been shown to be effective in the treatment of refractory ascites in a small pilot study [10]. However, considering the lack of large prospective studies, and the high risk of adverse events, outpatient administration of terlipressin cannot be recommended.

2.3.3 Other Treatments

Radiologists and surgeons have collaborated to develop a device, named alpha pump, that drains ascitic fluid into the urinary bladder [11]. The alpha pump has been recently tested in comparison with therapeutic paracentesis in a randomized clinical trial [11] confirming that it significantly reduces the need for paracentesis with an impact on quality of life, however, alpha pump was associated with a significant higher number of adverse events, among them, AKI after the intervention and the need of re-intervention. Finally, no survival advantages were observed [11].

Vaptans are vasopressin receptor antagonists and have been studied predominantly in heart failure but also in the setting of cirrhosis [12]. Their utility is treating hyponatremia and reducing fluid overload. These drugs appear to correct mild hyponatremia. Unfortunately, a recent meta-analysis showed no beneficial effect of vaptans in the control of ascites, moreover the treatment could be associated with an increased morbidity and mortality [12] therefore the use of this class of drug is not recommendable in clinical practice.

2.3.4 Transjugular Intrahepatic Portosystemic Shunts (TIPS)

TIPS decompresses the portal system like a side-to-side portocaval shunt inserted between the portal vein, at high pressure, and the inferior cava vein, at low pressure [13]. In the short-term, TIPS induces an increase of cardiac output, right atrial pressure, and pulmonary artery pressure leading to a secondary reduction in systemic vascular resistance and effective arterial blood volume [13].

International clinical guidelines recommends TIPS as a treatment of medically refractory ascites for patients who do not tolerate repeated LVP [1]. Indeed, LVP has a negative effect on systemic hemodynamics and renal function which often limits its use as a long-term treatment [6]. In contrast, TIPS offers a treatment option which even improves renal function and systemic hemodynamics as well. Within 4 weeks after TIPS, urinary sodium excretion and serum creatinine improve significantly and can normalize within 6–12 months. This is associated with an increase in serum sodium concentration, urinary volume, and glomerular filtration rate together with a normalization of plasma renin activity, aldosterone, and noradrenaline concentrations at 4–6 months of follow-up [13]. These findings strongly suggest that TIPS ameliorates central underfilling.

A recent analysis of the literature showed that TIPS was associated with better control of ascites and a higher incidence of hepatic encephalopathy (HE) than LVP, however results on survival were conflicting. This discrepancy, at least in part, could be explained by distinct selection criteria of the patients and the difference in the technical success rate of the procedures among different studies.

In the most recent randomized control trial, which included also patients with recurrent ascites, not just refractory, TIPS with covered stents improved survival when compared to LVP [14]. Furthermore, patients treated with TIPS had a lower rate of portal hypertension-related bleeding and fewer days of hospitalization than those treated with LVP [14].

Bercu et al. published a single center retrospective series of 92 patients with refractory ascites who underwent covered TIPS. Stents were initially dilated to 6 mm in an attempt to target a PSG of 7–12 mmHg [15]. If the porto-systemic gradient (PSG) response was not adequate (over the threshold of 12 mmHg indicating high risk of variceal bleeding/rebleeding), serial dilation up to the maximum stent diameter was performed. Of the 61 patients with documented follow-up, 90% had a partial or complete ascites response. The TIPS revision rate was 13%. Overall survival was 79% at 365-day follow-up and transplantation-free survival was 75%. Fifty-nine percent of patients had HE, of which 19.7% were severe. These recent investigations suggest TIPS as the primary therapy for the treatment of refractory ascites. Careful selection of patients with preserved liver function and the use of covered stents may further improve both survival and ascites control [13].

Unfortunately, the main limitation to the extensive use of TIPS for the treatment of refractory ascites is the presence of contraindications to TIPS placement, making TIPS use available for less than 40% of patients [13]. An important drawback is the risk of HE which remains frequent and constitutes an invalidating complication after TIPS allocation. This notwithstanding, recently Schepis et al. [16] showed, in a non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS and 53 patients who received TIPS dilated to its nominal diameter, that HE developed in a significantly lower proportion of patients with under-dilated TIPS (27%) than controls (54%) during the first year after the procedure (P = .015) without significant difference in the recurrence of ascites between groups. Hence, under-dilation of stent during TIPS placement may be feasible, associated with lower rates of HE, and effective in the ascites control. However these data need to be validated in adequately sized randomized controlled trials before an under-dilatation of TIPS can be routinely recommended in patients with ascites even more if we think that the lowest the PSG the lowest the risk of variceal bleeding which is lifethreatening.

3 Hyponatremia

Hypervolemic hyponatremia is common in patients with decompensated cirrhosis and is related to impaired solute-free water excretion secondary to non-osmotic hypersecretion of vasopressin (the antidiuretic hormone), a decrease in the delivery of pre-urine to the ascending limb of the loop of Henle (the diluting segment of the nephron), and the reduced production of prostaglandins, which results in a disproportionate retention of water relative to sodium retention [17]. Hyponatremia in cirrhosis is arbitrarily defined when serum sodium concentration decreases below 130 mmol/L [17]. Serum sodium concentration is an important marker of prognosis in cirrhosis and the presence of hyponatremia is associated with an impaired survival [17]. Moreover, hyponatremia may also be associated with an increased morbidity, particularly neurological complications, and reduced survival after transplantation [17].

3.1 Management of Hyponatremia

The aim of treatment of hypervolemic hyponatremia is to improve the free water excretion with the urine. The administration of hypertonic sodium chloride cannot be recommended since it would further increase ascites and edema. The current available treatments for hypervolemic hyponatremia in cirrhosis include: (1) fluid restriction, (2) albumin and (3) antagonists of AVP V2 receptors (vaptans). Fluid restriction to about 1 L per day has been suggested for these patients but its efficacy is poor [4]. Some reports suggest that albumin may increase the serum sodium concentration in patients with cirrhosis and ascites by increasing the effective circulating volume [18]. A number of evidences show that a short-therapy with vaptans (1 week to 1 month) ameliorates solute-free water excretion and leads to the increase in serum sodium levels in 45–82% of patients without particular side effects on renal function, urine sodium and circulatory function. Satavaptan and tolvaptan were investigated in the treatment of hypervolemic hyponatremia in cirrhotic patients [12]. Satavaptan was more effective than placebo in increasing the serum sodium concentration, but control of ascites was not improved even with an increased morbidity and mortality for unknown reasons [12]. Hence, satavaptan was abandoned. Tolvaptan was more effective than placebo in treating hyponatremia in patients with cirrhosis and ascites, however robust long-term data are still lacking [12]. Thus, nowadays the role of vaptans in the management of hyponatremia in cirrhosis is still uncertain.

4 Spontaneous Bacterial Peritonitis (SBP)

SBP is defined as bacterial infection of ascitic fluid without any intra-abdominal, surgically treatable source of infection [19]. The prevalence of SBP is about 20% in hospitalized patients with cirrhosis and ascites [20]. SBP is diagnosed when neutrophil count in ascitic fluid is ≥250 cells/μl [19]. The pathogenesis of SBP includes both a pathological bacterial translocation from the gut to the systemic circulation and an impaired ability of the local and systemic immunity to control the spread of these bacteria [19]. Bacterial translocation occurs because of an intestinal bacterial overgrowth, an increased intestinal permeability, a change in the quality of bacteria and the ineffective activity of the intestinal immune system [19]. SBP is associated with a high risk of AKI and poor short-term survival [20].

4.1 Management of SBP: Antibiotic Treatment

Empirical antibiotic therapy must be initiated immediately after the diagnosis of SBP, without the results of ascitic fluid culture [1, 4]. Cefotaxime, a third-generation cephalosporin, has been extensively investigated in patients with SBP because it covers most causative organisms and because of its high ascitic fluid concentrations during therapy [1, 4]. A dose of 4 g/day is as effective as a dose of 8 g/day [1, 4]. A 5-day therapy is as effective as a 10-day treatment [1, 4]. Alternatively, amoxicillin/clavulanic acid, first given intravenously then orally, has similar results with respect to SBP resolution and mortality, compared with cefotaxime [1, 4] and with a much lower cost. Ciprofloxacin, given either for 7 days intravenously or for 2 days intravenously followed by 5 days orally, results in a similar SBP resolution rate and hospital survival compared with cefotaxime, but with a significantly higher cost [1, 4]. Oral ofloxacin has given similar results as intravenous cefotaxime in uncomplicated SBP, without renal failure, hepatic encephalopathy, gastrointestinal bleeding, ileus, or shock [1, 4]. Cefotaxime or amoxicillin/clavulanic acid are effective in patients who develop SBP while on norfloxacin prophylaxis [1, 4]. In hospital acquired episodes of SBP, the efficacy of the above-mentioned antibiotics is poor, because those episodes are frequently sustained by multi-drug-resistant (MDR) bacteria; in this case a broader spectrum empirical antibiotic treatment should be used according to local epidemiology [3]. If ascitic fluid neutrophil count fails to decrease to less than 25% of the pre-treatment value after 2 days of antibiotic treatment, there is a high likelihood of failure to respond to therapy [3]. This should indicate modification of antibiotic treatment according to antibiogram or empiric choice or the presence of ‘secondary peritonitis’. Hepato-renal syndrome (HRS) occurs in approximately 30% of patients with SBP treated with antibiotics alone, and is associated with a poor survival [20]. The administration of albumin (1.5 g/kg at diagnosis and 1 g/kg on day 3) decreases the frequency of HRS and improves survival. It is unclear whether albumin is useful in the subgroup of patients with baseline serum bilirubin <4 mg/dL and creatinine <1 mg/dL [20]. Until further trials are completed, albumin infusion appears a valuable adjunction to the treatment of SBP.

4.2 Prophylaxis of SBP

The probability of SBP recurrence is about 70% at 1 year [1, 4]. In these patients, secondary prophylaxis with norfloxacin was shown to be effective in preventing the recurrence of SBP [1, 4]. Currently, primary prophylaxis of SBP is recommended in two conditions: (1) after episodes of gastrointestinal bleeding and (2) in patients with a protein concentration in ascitic fluid below 1.5 g/dl and advanced liver disease (Child-Pugh C9 and bilirubin ≥3 mg/dl or serum creatinine ≥1.2 mg/dl or serum sodium ≤130 mmol/l) [1, 4]. In patients with gastrointestinal bleeding and severe liver disease (at least two of the following: ascites, severe malnutrition, encephalopathy or bilirubin >3 mg/dl) ceftriaxone is the prophylactic antibiotic of choice [1, 4], while patients with less severe liver disease may be given oral norfloxacin or an alternative oral quinolone to prevent the development of SBP [1, 4]. In patients with a protein concentration in ascitic fluid below 1.5 g/dl, advanced liver disease and without prior SBP norfloxacin (400 mg/day) reduced the risk of SBP and improved survival [1, 4]. Therefore, these patients should be considered for long-term prophylaxis with norfloxacin.

Patients who recover from an episode of SBP have a high risk of developing recurrent SBP. In these patients, the administration of prophylactic antibiotics reduces the risk of recurrent SBP. Norfloxacin (400 mg/day, orally) is the treatment of choice [1, 4]. Nevertheless, this efficacy is counterbalanced by the risk of MDR infection, therefore the indication is for selected patients who cannot be addressed to alternative therapies. Alternative antibiotics include ciprofloxacin (750 mg once weekly, orally) or co-trimoxazole (800 mg sulfamethoxazole and 160 mg trimethoprim daily, orally), but evidence is not as strong as that with norfloxacin [1, 4]. Patients who recover from SBP have a poor long-term survival and should be considered for liver transplantation [1, 4].

5 Hepatorenal Syndrome (HRS)

Renal dysfunction is a severe complication of advanced stages of cirrhosis. Traditionally renal dysfunction in patients with liver disease has been defined as a serum creatinine >1.5 mg/dl [19] while AKI has been defined by an absolute increase of serum creatinine more than or equal to 0.3 mg/dl up to 48 h of clinical observation, or by a percentage increase of serum creatinine more or equal to 50% in less than seven days [19]. HRS has been defined as a syndrome that occurs in patients with advanced liver disease, characterized by impaired renal function and marked abnormalities in the arterial circulation and over-activity of the endogenous vasoactive systems. In the kidney, there is marked renal vasoconstriction that results in a low GFR. In the extrarenal circulation there is a predominance of arterial vasodilation that results in the reduction of systemic vascular resistance and arterial hypotension [20]. HRS has been traditionally classified into two different clinical types: type-1 HRS, characterised by a rapidly progressive reduction of renal function, defined by a doubling of the serum creatinine to a level >2.5 mg/dl in less than 2 weeks, and type-II HRS, in which the renal failure does not have a rapidly progressive course [20]. Recently this schematic classification has been questioned and partially modified as the reader can see in the guidelines of the European Association for the Study of the Liver published in 2018 for further details.

5.1 Management of HRS

The first measure is to minimize or to stop any potential nephrotoxic drug (i.e., diuretics, antibiotics, NSAIDs, angiotensin-converting enzyme inhibitors, etc.). Then, it is important to verify the presence of hypovolemia and, if present, to correct it. In patients with AKI stage ≥2 (increase of serum creatinine ≥2-fold from baseline) diuretics should be withdrawn and plasma expansion with albumin (1 g/kg of body weight) should be administered [1, 4, 20]. In patients without response of creatinine to albumin expansion HRS diagnosis should be considered whether there has been no recent use of nephrotoxic drugs, no hematuria, no significant proteinuria, no shock and no alterations of renal ultrasonography [1, 4, 20]. Liver transplantation (LT) is the best treatment both for type-1 and type-2 HRS [1, 4, 20]. Unfortunately, not all patients are eligible for LT. Thus, medical treatments have been developed, the most effective being the combination of vasoconstrictors plus albumin. The rationale behind the use of vasoconstrictors is to counteract splanchnic arterial vasodilation. Albumin improves the effective circulating volume [19]. Among vasoconstrictors, terlipressin (i.v. boluses starting from 1 mg/4–6 h to 2 mg/4–6 h or continuous i.v. infusion starting from 2 mg/24 h to 12 mg/24 h, increasing dosage in a stepwise fashion any 48–72 h in case of no response) is the most widely used, while alpha-adrenergic drugs have been claimed to be a potential alternative. Among alpha-adrenergic drugs, midodrine given orally (2.5 up to 12.5 qid) together with octreotide given subcutaneously (125 up to 250 μg bid) [20] or norepinephrine (continuous i.v. infusion starting from 0.5 to 3 mg/h) [20] has been used. Recently, terlipressin was shown to be superior to midodrine plus octreotide in the treatment of type-1 HRS [19]. Norepinephrine is as effective as terlipressin in terms of reversal of type-1 HRS and 1-month survival [20]. Albumin should be administered at a dose of 1 g/kg of body weight for 1 day followed by 20–40 g/day and it should be withdrawn or reduced if signs of pulmonary edema appear [20]. The treatment with vasoconstrictors plus albumin should be continued until serum creatinine reaches a value below 1.5 mg/dl. About 20% of patients may present a recurrence of HRS after treatment withdrawal, and retreatment is usually effective. Some patients may show a continuous recurrence of HRS at any attempt to discontinue terlipressin. For these patients, a high priority on the LT waiting list and/or outpatient infusion has been suggested [20]. The use of TIPS is a potential treatment because it reduces portal hypertension and increases cardiac output. TIPS improves renal perfusion, sodium and water excretion and has been reported to reduce serum creatinine in selected patients with HRS [20]. However, data available on the use of TIPS in patients with type-1 HRS are mainly based on case series and randomized clinical trials are needed to evaluate the use of TIPS in these patients. Both hemodialysis or continuous venous hemofiltration, have been used to treat patients with type 1 HRS [20]. However, published information is very scant and in most studies patients with type 1 HRS have not been differentiated from patients with other causes of renal failure.

6 Conclusions/Summary

Ascites is the most frequent complication of patients with portal hypertension. The first line of treatment is represented by diuretic therapy. Albumin, antibiotic therapy, TIPS constitutes a second line of treatment in highly selected patients with complicated ascites.