Introduction
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Ascites is one of the most common complications of liver cirrhosis, and 50%-60% of patients with liver cirrhosis will develop ascites within 10 years after diagnosis. After the first appearance of ascites, 10% of patients develop refractory ascites. Refractory ascites is associated with 65% 2-year mortality, poorer quality of life, and an increased risk of spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). Therefore, liver transplantation (LT) should be considered in any patient with refractory ascites. However, due to the long waiting period for LT, other treatment options must be considered, and the focus of treatment is to improve the patient’s quality of life and nutritional status.
Definition of refractory ascites
Ascites that cannot be resolved after treatment or that cannot be prevented by early recurrence of ascites by drug treatment, is called refractory ascites. Refractory ascites includes the following 2 distinct conditions:
➤Diuretic-resistant ascites: limiting sodium intake and administering maximum doses of Diuretics (spironolactone 400 mg and furosemide 160 mg) in response to ascites.
➤Diuretic-Refractory Ascites: Patients cannot be treated with diuretics because complications from diuretics preclude the use of effective doses.
Pathophysiology of ascites
Ascites is the result of a combination of portal hypertension and hepatic insufficiency. Ascites generally occurs when a portal pressure gradient exceeds 10 mmHg. In cirrhosis, portal pressure first increases due to increased resistance to portal blood flow at the level of the hepatic vascular bed. The increased resistance is due to altered liver architecture, as well as decreased vasodilation and increased vasoconstriction, resulting in increased intrahepatic vascular tone.
Secondary portosystemic collateral formation, splanchnic vasodilation leading to increased blood flow. Vasodilatation leads to a decrease in systemic vascular resistance and an insufficiency of effective arterial blood volume. Increased cardiac output, activation of the sympathetic nervous system, antidiuretic system, and the renin-angiotensin-aldosterone system aim to correct effective hypovolemia, but can lead to renal vasoconstriction and sodium and water retention.
Hypoalbuminemia due to hepatic insufficiency is the cause of decreased colloid osmotic pressure, leading to fluid leakage into the interstitial region.
Advanced liver cirrhosis is an inflammatory state with high levels of pro-inflammatory cytokines, which can increase arterial nitric oxide production and aggravate splanchnic blood vessels dilation, which in turn leads to insufficient filling of the effective arteries. Decreased effective volume easily develops into refractory ascites. Bacterial translocation following gut dysbiosis and increased gut permeability is common and contributes to the release of proinflammatory cytokines.
Management of refractory ascites
One of the most important treatments for refractory ascites is to treat the underlying liver disease (abstinence from alcohol, antiviral therapy, etc.), which can lead to resolution of the ascites. In randomized studies comparing transjugular intrahepatic portosystemic shunt (TIPS) with repeat aspiration aspiration, up to 20% of patients did not require further high volume aspiration aspiration, possibly because the etiology was controlled , portal hypertension and/or liver function improved.
Diuretics are often discontinued in patients with refractory ascites. European guidelines recommend that diuretics be discontinued if urinary sodium is below 30 mmol per day during diuretic therapy.
Blood pressure and renal function should be closely monitored for reduced organ perfusion or hypotension (systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, Patients with acute kidney injury, SBP) should consider discontinuing or not using beta-blockers.
Volume aspiration and albumin infusion< /strong>
Large volume aspiration plus albumin infusion (LVP+A) is the standard and first-line treatment for tension ascites . This method provides quick relief from bloating, pain and discomfort, and can be performed on an outpatient basis. However, recurrence of ascites is the norm, as this is only a topical treatment and has no beneficial effect on any of the mechanisms involved in ascites formation.
Transjugular Intrahepatic Portosystemic Shunt
TIPS Yes A lateral-to-lateral portocaval shunt in the liver connecting the main branch of the portal vein to the great hepatic vein. It reduces ascites formation by reducing portal pressure, temporarily increasing effective arterial blood volume, and simultaneously depressurizing the portal venous system and hepatic microcirculation, reducing lymph formation. Reduced plasma renin activity, plasma aldosterone, and norepinephrine concentrations after TIPS implantation improved renal perfusion.
Automatic low-flow ascites pump
The automatic low-flow ascites pump (alfapump system) consists of a subcutaneously implantable rechargeable device that transfers ascites from the peritoneal cavity to the bladder, through which Drain the ascites slowly and continuously every day. The amount of ascites to be removed each day can be adjusted. However, automatic low-flow ascites pumps have been associated with renal impairment due to activation of the vasoconstrictor system.
Liver Transplant p>
Patients with refractory ascites should be evaluated for LT immediately after diagnosis, because LT is the only way to treat the underlying liver disease and improve long-term prognosis. LT is the only treatment option for patients with high MELD or Child-Pugh scores, and for patients with pre-existing recurrent or chronic hepatic encephalopathy. While waiting for treatment, the TIPS or alfapump system should be used.
Other treatment options< /p>
Albumin infusion: Albumin can function as a plasma expander and also as a potent scavenger, anti-inflammatory and antioxidant molecule to keep the body balance.
Vasopressors: Vasoconstrictors have been studied in reducing the incidence of postoperative circulatory dysfunction (PPCD), but data exist dispute.
vasopressin receptor antagonists: Vaptans are selective oral vasopressin v2 receptor antagonists for the treatment of isovolumic Sexual or hypovolemic hyponatremia.
Summary
Severe refractory ascites is characterized by a poor prognosis, and LT must be considered first, and TIPS should be considered in eligible patients if there are contraindications or if the waiting time for LT exceeds 6 months. When TIPS is not feasible, the effects of alfapump or LVP+A on risk-benefit balance and quality of life may be considered. Regardless of the treatment option chosen, careful patient selection is critical to avoid further decompensation and complications with each therapy.
Yimaitong compiled from: Larrue H, Vinel JP, Bureau C. Management of Severe and Refractory Ascites[J]. Clin Liver Dis. 2021 May;25(2):431-440.
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