Application of albumin in liver cirrhosis and its complications
This article reviews the physiological characteristics and functions of human albumin alongside its clinical application for cirrhosis and associated complications in hepatology
Huibo Li Suodi Zhai PhD Department of Pharmacy , Peking University Third Hospital , Beijing , China ; Institute for Drug Evaluation , Peking University Health Science Center , Beijing , China
Article reprinted from Clinical Medication Journal Vol . 16 , No . 01 , Jan 2018 , with kind permission
The clinical application of human albumin as a pharmaceutical product first traces back to World War II when it was used for fluid resuscitation . Hypoalbuminaemia is considered to be one of the common metabolic manifestations in surgical and critical patients and relates to poor prognosis . Therefore , exogenous albumin supplementation has become a routine and reasonable method to correct hypoalbuminaemia . With further understanding of the complex structure and physiological functions of albumin , its use has been extended to blood volume expansion , treatment of shock and burns , 1 and ovarian hyperstimulation syndrome . 2
Since the publication of a systematic review by the Cochrane Collaboration Network in the BMJ in 1998 , 3 there has been continued controversy around the clinical safety and efficacy of human albumin in the treatment of critical patients . In 2004 , the large multicentre , randomised , controlled SAFE study , published in the New England Journal of Medicine , which included nearly 7000 critical patients requiring volume expansion , confirmed the safety and effectiveness of albumin for volume expansion for critical patients . 4 In the same year , a systematic review published in Critical Care Medicine included 71 randomised , controlled trials ( RCTs ) including the SAFE study , and suggested that albumin treatment could reduce all-cause mortality ( relative risk ( RR ) = 0.92 ; 95 % CI : 0.86 – 0.98 ). 5 As the quality of systematic reviews depends on the reliability of the methodological design and the quality of the included RCTs , the argument on albumin also reflects a process of evolution and continuous improvement of evidence-based medicine .
Patients with liver cirrhosis are prone to developing hypoalbuminaemia owing to a decrease in the amount of albumin synthesised by liver cells , decreased albumin concentration as a result of water and sodium retention , and other factors such as increased capillary permeability . Liver cirrhosis patients might be almost asymptomatic owing to liver compensation in the early stage . In the decompensation stage , patients may develop complications such as portal hypertension , ascites , spontaneous bacterial peritonitis ( SBP ), gastrointestinal bleeding , hepatic encephalopathy ( HE ), hepatorenal syndrome ( HRS ) and septic shock .
Physiological properties of albumin Structure of albumin Albumin is the most common component of plasma protein ( 35 – 50g / l ), which accounts for about 50 % of the total plasma protein . It is a non-glycosylated , negatively charged small molecule composed of 585 amino acids , with a molecular weight of 66.5 kDa . It has a ‘ heart-like ’ tertiary molecular structure ; 67 % of the tertiary structure is composed of alpha supercoil . The entire albumin molecular is divided into three domains ( I – III ) which , individually , further consist of two subdomains : A and B . The A and B subdomains can transform between each other through the flexible ring of a proline residue , which helps albumin to bind with small molecules . 6 There are 35 cysteine residues in the albumin molecule , of which 34 are bound as disulfide bonds . The thiol group formed by the cysteine residue at position 34 forms a redox group ( Cys-34 ). It can bind with substances such as reactive oxygen species ( ROS ) derived from the aerobic metabolites in the body to play an antioxidant role ( Figure 1 ).
Figure 1 . Structure of albumin
Synthesis , distribution and metabolism of albumin Albumin is synthesised in the liver ( 10 – 15g / d ) and released into the systemic circulation . Its synthesis is affected by hormone factors such as insulin , cortisol and growth hormone . Proinflammatory mediators can inhibit its synthesis . A total of 30 %– 40 % of albumin is distributed in the blood , and the rest enters the interstitial space through capillaries and
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