The development of ascites is associated with a reduction in 5-year survival, from 80% to 30%, largely associated with complications including infection and hepato-renal syndrome (HRS).
Diagnosis of ascites requires a thorough evaluation to exclude other etiologies, such as heart failure, kidney failure, infections or malignant neoplasms.
The complete workup consists of laboratory evaluation, abdominal Doppler ultrasound, and diagnostic paracentesis, although data do not currently support this recommendation.
A serum ascites albumin gradient ≥11 g/dL suggests portal hypertension, massive liver metastases, or right heart failure. In addition to patients with symptoms suggestive of infection (e.g., fever, abdominal pain), cultures of ascitic fluid should be obtained in any decompensated patient, including the development of encephalopathy or acute kidney injury or jaundice.
| Management of ascites |
In general, angiotensin II receptor antagonists, angiotensin-converting enzyme inhibitors (ACE inhibitors), and nonsteroidal anti-inflammatory drugs should be avoided in patients with ascites due to the impact on effective circulating volume and renal perfusion. Although ACEIs or angiotensin II receptor antagonists are not directly nephrotoxic, it has been observed that in cirrhotic patients with ascites they correlate with a higher risk of end-stage renal disease.
Depending on the response to treatment, ascites can be classified as receptive, recurrent, or refractory.
Initial management of ascites includes sodium restriction to 2 g. For diuresis, it is suggested to start with 100-200 mg/day of spironolactone and then make dose adjustments at intervals of at least 72 hours, until reaching a maximum dose of 400 mg/day.
For recurrent ascites, combination therapy of furosemide and spironolactone is indicated, with an initial dose of 40 mg/day of furosemide up to a maximum dose of 160 mg/day.
Once the ascites has mobilized, diuretics should be reduced to the lowest effective dose to minimize adverse effects.
In some cases (approximately 5-10% of patients with cirrhosis), ascites cannot be managed medically and becomes refractory, with 50% survival at 6 months.
Refractory ascites occurs when 1 of the following 3 criteria is met: a) grade 2 or 3 recurrence within 4 weeks of mobilization with diuretic therapy (early recurrence), b) persistence despite maximum diuretic dose ( resistant to diuretics) or, c) recurrence or persistence of side effects when trying to increase diuretics (intolerant to diuretics).
Large-volume therapeutic paracentesis (>5 liters) can be used for refractory ascites , with fewer side effects than forced diuresis. Removal of large amounts of fluid, particularly >8 liters, can lead to post-paracentesis circulatory disturbances and dysfunction, manifesting as HRS, hepatic encephalopathy, or dilutional hyponatremia. To mitigate this risk, the infusion of 6-8 g of albumin/liter of ascitic fluid removed is recommended.
Non-selective β-blockers, used in the management of portal hypertension, are associated with a higher incidence of post-paracentesis circulatory dysfunction, although there is insufficient evidence to oppose their use in cirrhosis. However, caution is advised in case of renal failure, hyponatremia or hypotension.
> Transjugular intrahepatic portosystemic shunt
This is a useful therapeutic placement procedure for the treatment of refractory ascites in certain patients, particularly those with lower scores on the Model for End-stage Liver Disease and confirms a 93% probability of 1-year transplant-free survival in compared to 53% for patients managed with paracentesis, diuretics and albumin. After placement, it may take up to 6 months before the ascites resolves. Salt restriction should continue after the procedure.
It is recommended to discontinue treatment with diuretics to allow the return of splanchnic volume to the systemic circulation.
Despite the good results in patients with a low liver disease score in the aforementioned Model, scores ≥18 are generally considered high risk to undergo this procedure. Patients not suitable for this treatment should be referred to receive a liver transplant.
> Hyponatremia and hepatic hydrothorax
This condition is also common in the presence of cirrhosis. It is defined by a serum sodium <135 mEq/l. In 49% of cirrhotic patients, hyponatremia is associated with severe ascites and frequent ascites complications.
The most common subtype is hypervolemic hyponatremia secondary to third space and vasopressin activation, while hypovolemic hyponatremia can occur with the use of diuretics.
The sodium correction rate is based on the acuity with which the target rate of increase in serum sodium occurs, for chronic cases of 4-6 mEq/L over 24 hours. In acute cases, correction should be faster, although the guidelines do not specify the exact rate. Specific management of hyponatremia is based on severity:
• Mild hyponatremia (126–135 mEq/l). It can be monitored.
• Moderate hyponatremia (120–125 mEq/l) with hypervolemia. It can be managed with fluid restriction and diuretics. Vaptans (vasopressin receptor antagonists) have limited use due to high cost and should not be used beyond 30 days. Normal saline and low-dose diuretics are indicated for hypovolemic patients.
• Severe hyponatremia (<120 mEq/l). It can be managed with infusion of concentrated albumin. Hypertonic saline is considered in limited subsets of patients, in the critical care or peritransplant setting. Hepatic hydrothorax, a complication of cirrhosis that is difficult to manage, is a pleural effusion (transudate) resulting from the translocation of peritoneal fluid through diaphragmatic defects.
It has been reported to occur in 4% to 12% of patients with cirrhosis. Although it typically occurs in the right hemithorax, it can also occur in the left or bilaterally, in the absence of ascites. It is associated with a higher risk of mortality, higher than that predicted by the End-Stage Liver Disease Model score.
Management is similar to that of ascites, with fluid restriction and diuresis. Abdominal hernias, particularly umbilical hernias, are common in the setting of ascites due to increased intra-abdominal pressure. When the management of ascites and nutritional status have been optimized, surgical repair of the hernia can be considered.
| Spontaneous bacterial peritonitis |
The most common source of bacterial infections in patients with cirrhosis is spontaneous bacterial peritonitis (SBP), which accounts for 27% to 36% of infections. In the event of clinical deterioration (jaundice, altered mental activity or acute kidney injury), SBP must be excluded by means of a diagnostic paracentesis.
In hospitalized patients, diagnostic paracentesis should be performed even in the absence of symptoms suggestive of SBP.
The diagnosis of SBP is established when the absolute neutrophil count in the ascitic fluid is >250 cells/mm3 and confirmed by positive cultures.
The mainstay of management of SBP and spontaneous bacterial empyema is the empirical administration of intravenous antibiotics after cultures have been obtained, since each hour of delay in treatment increases mortality by 10%.
Effective empiric antibiotic choice plays a key role in the timely management of SBP. Third-generation cephalosporins are effective if the local prevalence of multidrug-resistant organisms is low, while coverage therapy (i.e., piperacillin-tazobactam with vancomycin) is recommended when there is a high prevalence of multidrug-resistant organisms. history of infection by multidrug-resistant organisms, nosocomial infections acquired in the hospital or, critical illnesses.
If there is a history of vancomycin-resistant Enterococcus , daptomycin should be added. Positive cultures with neutrophil counts <250 cells/mm3 create some confusion; In such cases, antibiotics are not required and contamination probably occurred. In addition to antibiotics, 1.5 g/kg of albumin should be administered on day 1 and 1 g/kg on day 3, given its special usefulness in the presence of acute kidney injury or jaundice.
To evaluate response to treatment, paracentesis/thoracentesis can be repeated after 2 days of therapy. Treatment and secondary prophylaxis should be done with norfloxacin, or with ciprofloxacin if norfloxacin is not available.
For cases of bleeding, gastroenteritis, prophylaxis is done with intravenous ceftriaxone 1g/24 hours for 7 days. Primary SBP prophylaxis should also be indicated in the following cases of cirrhosis without bleeding:
• Ascitic protein <1.5 g/l
• Renal dysfunction (serum creatinine ≥1.2 mg/dl, blood urea nitrogen >25 mmol/l or serum sodium <130 mEq/l) • Liver failure with Child-Turcotte-Pugh mortality predictive score >9 (severity determined by a higher score ranging from good liver function (5 points) to advanced liver dysfunction (15 points), or bilirubin >3 mg/dl.
| Acute kidney injury |
Patients with cirrhosis and ascites are at risk of kidney injury (creatinine increase ≥ 0.3 mg/dL within 48 hours or ≥50% creatinine increase over 7 days), with an estimated prevalence in hospitalized patients between 27% and 53%. The 2 most common acute kidney injuries are prerenal uremia and acute tubular necrosis.
Prerenal uremia may be secondary to hypovolemia or HRS. The diagnosis of HRS is made after excluding hypovolemia and shock, exposure to a nephrotoxic agent, and structural kidney damage in a patient with ascites who presents with prerenal acute kidney injury.
The main treatment for HRS is vasoconstrictors and albumin for up to 14 days. In the US, HRS treatment includes combined midodrine and octreotide, although their efficacy is low.
The preferred treatment is terlipressin , a vasoconstrictor that can be used outside the intensive care unit, which improves the likelihood of reversal of HRS without dialysis. Recently, protocols are being developed in some US centers to be used in the treatment of HRS.
An alternative with comparable efficacy is norepinephrine , although its use is limited to the intensive care unit. Some studies have investigated vasopressin as a substitute for octreotide, and it was found to be associated with improved survival and recovery, although so far its use in the US is limited.
Response to therapy can be defined as decrease in creatinine to <1.5 mEq/L or within 0.3 mEq/L of baseline. If despite using the maximum doses of therapy for 4 consecutive days a response is not observed, then the vasoconstrictors may be discontinued.
If there is no response to treatment, renal replacement therapy is reserved for transplant candidates, or those who present reversibility of the dysfunction of other organs. In patients with limited expectations of renal recovery, dual liver and kidney transplantation may be considered.
