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Albumin in decompensated cirrhosis : Future concepts and prospects

This article discusses the concept and characterisation of decompensated cirrhosis and the future role of albumin in its management , including long-term administration
Rahul Kumar MBBS MD FRCP ( Edin ) FAMS ( Singapore ) Director , Hepatology Services Consultant , Dept of Gastroenterology & Hepatology Changi General Hospital , Singapore
Wong Yu Jun MD MMed MCI FRCP ( Edin ) FAMS ( Singapore ) Consultant , Dept of Gastroenterology & Hepatology Changi General Hospital , Singapore
Albumin is the main circulating protein in healthy adults and is exclusively synthesised within the liver . 1 It is a small protein of 65kDa and comprises two sub-domains . Once produced , up to 40 % of albumin is released into the bloodstream . The half-life of albumin ranges from 12 to 19 days . 2 The serum albumin level is often reduced in decompensated cirrhosis due to reduced production and increased loss resulting from underlying disease and various therapeutic interventions .
Albumin has both oncotic and non-oncotic properties . 1 Its well-established oncotic property as a plasma expander is attributed to its high plasma concentration and the Gibbs- Donnan effect . 3 Recent evidence suggests that the effect of albumin goes beyond the oncotic and transport functions , but also includes immunomodulatory and antioxidant functions . Albumin is shown to attenuate prostaglandin E2-mediated immune-dysfunction in patients with decompensated cirrhosis . 4 It also exerts an immunomodulatory effect by downregulating the expression of tumour necrosis factor-alpha and pro-inflammatory nuclear factor-kappa B . 5 Another property attributed to albumin is as an antioxidant to scavenge reactive oxygen and nitrogen species in the body . 6
The concept of decompensated cirrhosis Cirrhosis represents the common pathway of progression of all chronic liver diseases . Transition from compensated to decompensated cirrhosis is an important watershed moment . It has been shown that survival is significantly reduced ( from 12 years to 2 years ) when compensated cirrhosis transitioned into decompensated cirrhosis . 7
Characterisation Decompensated cirrhosis is characterised by chronic inflammation and severe portal hypertension , leading to systemic circulatory dysfunction . 1 As a corrective response to portal hypertension , excessive nitric oxide secretion results in both splanchnic and arterial vasodilatation , which subsequently impairs organ perfusion . 8 To ensure adequate organ perfusion , the arterial pressure is maintained by increased activity of the renin – aldosterone – angiotensin system . 9 A better understanding of circulatory dysfunction in patients with decompensated cirrhosis has led to the use of albumin and vasoconstrictors to improve circulatory dysfunction and prevent kidney injury . 9
Albumin in decompensated cirrhosis Hypoalbuminaemia is a known predictor of poor survival in decompensated cirrhosis and serves well as a constituent of the Child-Turcotte-Pugh score . 1 What is less well appreciated is the fact that abnormalities with serum albumin in decompensated cirrhosis patients are both quantitative and qualitative . 1 The quantitative reduction in serum albumin concentration is a result of dilution from sodium and water retention , reduced synthesis from hepatocytes , as well as increased trans-capillary leak , particularly among patients with refractory ascites . 10 The quality of albumin is further compromised in decompensated cirrhosis due to a higher proportion of oxidised albumin . 11 The oxidised albumin differs from native albumin because it has a lower binding capacity , impaired antioxidant properties and a shortened half-life . 11
Current indications for albumin in decompensated cirrhosis The currently approved indications for human albumin include large volume paracentesis , spontaneous bacterial peritonitis , and hepatorenal syndrome . 12
Large volume paracentesis ( LVP ) LVP is a common therapeutic option for decompensated cirrhosis with refractory ascites . Paracentesis-induced circulatory dysfunction ( PICD ) is a known complication of LVP . The reported incidence ranges from 17.1 % to as high as 72.7 %. 1 While PICD can lead to hypotension with resultant renal impairment , readmission and mortality , human albumin infusion in cirrhosis patients undergoing LVP was associated with a lower risk of PICD . 13 Current guidelines recommend albumin replacement during LVP beyond 5l to prevent PICD . 12
Spontaneous bacterial peritonitis ( SBP ) SBP is defined based on the presence of > 250 polymorphonuclear cells / mm 3 or positive ascitic fluid cultures , in the absence of an intra-abdominal source of infection or malignancy . 7 Albumin infusion , in addition to cefotaxime , significantly reduced the risk of renal impairment ( 33 % vs 10 %), inpatient mortality ( 29 % vs 10 %) and 3-month mortality ( 41 % vs 22 %). 14 The benefits of albumin were subsequently confirmed in a meta-analysis of randomised trials , especially in patients at high risk of developing renal impairment ( baseline serum bilirubin ≥ 4mg / dl or creatinine ≥1mg / dl ). 15
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