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Treatment of hypoalbuminaemia in severe liver diseases

Severe liver diseases have complex pathological mechanisms and lead to a variety of adverse clinical outcomes . Patients with severe liver disease can benefit from infusion of human albumin because of its colloid capacity substitution effects and biological pleiotropy .
Zhao Dandan Nan Yuemin Department of Integrated TCM & Western Medicine of Hepatology , The Third Hospital of Hebei Medical University , China ; Hebei Provincial Key Laboratory of Mechanism of Liver Fibrosis , China
Severe liver disease refers to severe hepatic injury resulting from different causes , such as decompensated liver cirrhosis , hepatic failure , synthesis disorders , and detoxification , metabolic and bioconversion dysfunctions of the liver . In these cases , the physiological needs of the body cannot be met . The case fatality rate is > 50 % in patients who do not receive liver transplantation . 1 , 2 Studies have shown that of patients with > 10-year history of liver cirrhosis , 50 % had ascites or spontaneous bacterial peritonitis ( SBP ), 45 % had hepatic encephalopathy and 40 % had oesophageal and gastric varices . Of patients with a history of ascites of > 5 years , 39 % had acute renal injury / hepatorenal syndrome . Approximately 25 %– 35 % of patients with cirrhosis had infections , 19 % had hepatic failure , and 5 %– 8 % had hepatocellular carcinoma ( HCC ). Portal hypertension , hypoalbuminaemia , lowered immunity and hyponatraemia are major pathophysiological causes of complications of severe liver disease . Standard medical treatment and correction of hypoalbuminemia are of great importance to improve prognosis .
Synthesis and role of albumin Albumin is synthesised by hepatic cells and its normal concentration in the body is 3.5 – 5.0g / dl , accounting for 50 % of plasma protein . It has a molecular weight of 66 kDa and is composed of 585 amino acids . 3 Its half-life is approximately 16 – 18 hours . Human albumin , as a drug , carries highenergy negative charges and is present in a high concentration in blood , and these features form the basis of blood volume adjustment . 4 Albumin helps maintain colloid osmotic pressure and transports non-water-soluble compounds . In addition , the capacity of human albumin to bind to reactive oxygen , metals and bilirubin confers an ability to scavenge free radicals and antioxidative properties . Furthermore , it has detoxifying effects , effects on reprocessing metabolites and increasing cellular glutathione levels , decreases NF-κB activation , and inactivates endotoxin , thereby conferring effects on inflammatory responses , immunoregulatory functions and endothelial stabilisation .
Patients with liver cirrhosis experience severe hypoalbuminaemia owing to the decreased ability of the liver to synthesise albumin , insufficient protein intake and disorders of digestion and absorption , increased permeability of the vascular wall , albumin exudation due to chronic inflammation , and dilution of the blood and extracellular fluid from water – sodium retention caused by aldosterone and decreased ADH inactivation . 5 Currently , there is not a precise definition of hypoalbuminaemia . Generally , patients with serum albumin < 35g / l are considered hypoalbuminaemic . Concentrations < 25g / l are considered clinically significant . 6 Hypoalbuminaemia in patients with liver cirrhosis is an important factor for worsening of ascites , infection , hyponatraemia , hepatorenal syndrome ( HRS ) and hepatic dysfunction , seriously influencing long-term survival rate of patients .
The main objectives of using human albumin in severe liver disease is to regain blood volume and treat complications of liver cirrhosis . Albumin can prevent post-paracentesis circulatory dysfunction ( PPCD ), prevent renal failure after SBP while treating ascites , and improve renal microcirculation as a peripheral vasoconstrictor in treating HRS . 7 Human albumin is a blood product so should not be used in patients with a history of allergy . Attention should be paid to potential adverse reactions during its use , such as fever , flushing , urticaria , nausea , and increased blood volume . Therefore , albumin should be used with caution in patients with serious anaemia , heart failure and hypertension .
Clinical applications in severe liver disease Ascites Albumin has been used widely in clinical practice since the 1940s , but no consistent conclusion on the rationales for treatment and safety have been drawn . The 2017 Chinese Guideline for Diagnosis and Treatment of Ascites in Patients with Hepatic Cirrhosis and Relevant Complications states that human albumin ( 20 – 40g / d ) can improve the prognosis of patients with liver cirrhosis and ascites , especially refractory ascites and SBP . Large volume paracentesis ( LVP ) ( 4- 5l / d ) combined with human albumin ( 4g / l ascites ) is an effective method for treating refractory ascites . 9 As stated in the EASL Clinical Practice Guidelines for the Management of Patients with Decompensated Cirrhosis in 2018 , patients who undergo LVP > 5l should receive albumin infusion ( 8g / l ) for plasma volume expansion and other expanders are not recommended . Patients with LVP < 5l should receive albumin therapy . For refractory ascites , repeated LVP + albumin ( 8g / l ) is recommended as first-line treatment regimen . 10 LVP without expansion is the leading cause for PPCD . Expansion is the optimal therapy for preventing PPCD . HA infusion can be given after LVP to improve circulation . 5 A meta-analysis showed that as compared to other treatments , HA infusion after LVP not only reduced the incidence of PPCD ( 66 %) and hyponatraemia ( 42 %), but also decreased the case fatality rate ( 36 %) of patients , showing significant efficacy . 11
The ANSWER study , investigating long-term use of albumin in the treatment of ascites in patients with liver cirrhosis was published in 2018 and
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