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Interpretation of 2021 "Expert Consensus on the Application of Human Albumin in Critically Ill Patients"
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 Albumin is a spherical water-soluble protein, rich in aspartic acid and glutamic acid residues, and negatively charged.
It is the most abundant protein in serum and extracellular fluid, accounting for about half of all serum proteins
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Albumin is only synthesized by liver cells, translated into prealbumin, and transported to the Golgi apparatus after excision of the N-terminal propeptide through the endoplasmic reticulum, and continues to be secreted into the blood, so the liver is an important place for albumin synthesis and metabolism [1]
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Important complications of liver cirrhosis include varicose bleeding, hepatic encephalopathy, hepatorenal syndrome (HRS) and infection.
The ICU often treats patients with severe liver failure and extrahepatic organ failure caused by cirrhosis.
These patients will The ICU accepts organ support treatment and also provides preoperative management for patients preparing for liver transplantation (LT) [2]
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A meta-analysis of 2523 patients found that the mortality, hospital mortality and 6-month mortality of patients with liver cirrhosis during ICU treatment were as high as 42.
7%, 54.
1% and 75.
1% [3]
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At the same time, liver cirrhosis can lead to reduced albumin production and impaired function, and low albumin levels are associated with an increased risk of death in hospitalized patients with liver cirrhosis [4,5]
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Although human albumin has been widely used clinically to increase the serum albumin level of patients with liver cirrhosis, there is currently no unified standard for its use
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In July 2021, the "Expert Consensus on the Application of Human Albumin in Critically Ill Patients" published in the English Edition of the Chinese Medical Journal (CMJ) gave the timing and effect of the application of human albumin in adult ICU patients with severe liver cirrhosis.
Recommended
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Recommendations 21 In ICU patients with severe liver cirrhosis and large amounts of ascites, it is recommended to infusion of albumin (Grade 2+, weak recommendation) after peritoneal puncture (LVP) [1]
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At present, LVP is the first choice for treatment of liver cirrhosis and massive ascites.
Infusion of albumin can reduce the incidence of circulatory dysfunction (PICD) after abdominal puncture
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 In 2018, the ANSWER (ascites in patients with hepatic cirrhosis) study of a large sample of RCT included 440 patients with liver cirrhosis and ascites.
The results found that: compared with the standard treatment group, the risk of refractory ascites in the albumin combined standard treatment group Reduced by 57%, the 18-month survival rate was significantly higher, and the risk of death was also reduced by 38% [6]
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Bernardi et al.
's meta-analysis included 1225 patients (17 RCTs) with liver cirrhosis and found that compared with other alternative therapies, the incidence of PICD in the albumin infusion group after LVP was reduced by 61%, and the mortality rate was reduced.
36%
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Compared with untreated patients, albumin infusion can reduce the incidence of circulatory dysfunction after puncture in patients with liver cirrhosis and tension ascites
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Compared with other treatment options, albumin treatment can significantly reduce the incidence of other complications in patients with liver cirrhosis, especially the risk of ascites recurrence, kidney damage, and rehospitalization [7]
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However, some foreign meta-analysis showed that albumin infusion after LVP did not significantly reduce the mortality rate, and albumin treatment did not reduce the mortality rate of patients with liver cirrhosis [8,9,10]
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Consensus analysis, the reason for the different results may be that these meta-analysis included two controversial studies, including the control group of Ginès et al.
was a diuretic study [11], and the control group of Zhao et al.
was mannitol.
Research [12]
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If you exclude these two studies, you can still get the conclusion that albumin treatment can significantly reduce mortality
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Therefore, in ICU patients with liver cirrhosis and large amounts of ascites, infusion of albumin after LVP can reduce the risk of refractory ascites, reduce the incidence of PICD, and improve the survival rate [5]
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Recommendation 22 recommends the use of human albumin combined with terlipressin to treat hepatorenal syndrome (HRS) and reduce acute kidney injury (AKI) (Grade 2+, weak recommendation) [5]
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Renal damage in patients with liver cirrhosis includes acute kidney injury (AKI), hepatorenal syndrome-acute kidney injury (HRS-AKI), hepatorenal syndrome-non-acute kidney injury (HRS-NAKI), and chronic kidney disease (CKD)
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Among them, AKI is one of the serious complications of patients with decompensated liver cirrhosis
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The incidence of AKI in hospitalized patients with liver cirrhosis can be as high as 20% to 80%, and they are more likely to progress to renal failure, with a high mortality rate [13]
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Recently, drug therapy related to type I HRS has achieved satisfactory results.
In addition to the application of albumin to increase renal perfusion, vasoconstrictor drugs such as terlipressin can also be used [13]
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AKI is one of the serious complications of patients with decompensated liver cirrhosis.
The incidence of AKI in hospitalized patients with liver cirrhosis is as high as 20% to 80%, and such patients are more likely to progress to HRS and have a higher mortality rate [14]
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Human albumin combined with terlipressin can effectively reduce blood creatinine levels, treat HRS, and reduce mortality
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The 2021 RCT included 300 patients with type I HRS, and defined two consecutive serum creatinine ≤ 1.
5 mg/dL (132.
6 μmol/L) (at least 2 hours between the two measurements) as HRS reversal.
The result was that albumin combined with Triga The HRS reversal of the vasopressin group and the albumin alone group were 32% and 17%, respectively; in patients with systemic inflammatory response syndrome, the HRS reversal of the two groups were 37% and 6%, respectively [15]
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In 2017, a study by Facciorusso et al.
included 13 RCTs and a total of 739 patients with type I HRS, and found that compared with albumin therapy alone, albumin combined with terlipressin treatment may cause short-term mortality in patients with type I HRS Decrease [16]
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Another meta-analysis included 13 RCTs and a total of 770 HRS patients, and defined HRS remission as a decrease in serum creatinine value of more than 50% or ≤1.
5 mg/dL (132.
6 μmol/L) compared with before treatment.
The results found that: Compared with the albumin group or albumin combined with midodrine and octreotide, the albumin combined with terlipressin treatment group had a higher HRS remission rate, but there was no significant benefit in terms of HRS recurrence and mortality [17]
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In 2019, a meta-analysis included 25 RCTs and a total of 1263 HRS patients.
The analysis found that the albumin combined with terlipressin group had a better cure rate than the albumin combined with midodrine and octreotide, and albumin combined with octreotide.
High, but there is no significant difference in mortality between the groups [18]
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In addition to treating HRS, albumin therapy can also reduce the risk of kidney damage in patients with liver cirrhosis
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In 2021, an RCT involving 777 patients found that the albumin treatment group had a lower incidence of renal damage and a lower mortality rate than the standard treatment group [19]
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Therefore, the consensus recommends that albumin combined with terlipressin be used to treat HRS in decompensated liver cirrhosis to reduce patient mortality
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 Summary For patients with liver cirrhosis, early detection, prevention, and early treatment should be advocated to prevent disease progression and avoid clinical decompensated complications
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Especially for many patients with liver cirrhosis, traditional drug therapy is the cornerstone of the treatment of liver cirrhosis [13], and albumin has also been increasingly used in the treatment of severe liver cirrhosis
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The "Expert Consensus on the Application of Human Albumin in Critically Ill Patients" further recommends that in ICU patients with severe liver cirrhosis and large amounts of ascites, infusion of albumin is recommended after LVP
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It is also recommended to use human albumin combined with terlipressin to treat HRS to reduce AKI
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 References: [1] Zhang Chenxi, Cao Zhujun, Xie Qing.
New understanding of albumin in the treatment of decompensated liver cirrhosis[J].
Liver,2021,26(05):479-483.
[2] Dong V, Karvellas CJ.
Acute-on-chronic liver failure: objective admission and support criteria in the intensive care unit.
JHEP Rep 2019;1:44–52.
[3] Weil D, et al.
Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis.
Ann Intensive Care 2017;7:33.
[4] Valerio C,et al.
Human albumin solution for patients with cirrhosis and acute on chronic liver failure: Beyond simple volume expansion.
World J Hepatol 2016 ;8:345–354.
[5] Yu YT, Liu J, Hu B, et al.
Expert consensus on the use of human serum albumin in critically ill patients.
Chin Med J (Engl).
2021;134(14): 1639-1654.
[6] Caraceni P,et al.
Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.
Lancet 2018;391:2417–2429.
[7] Bernardi M, et al.
Hepatology.
2012 Apr;55(4)1172-81.
[8] Kütting F,et al.
Insuffificient evidence of benefifit regarding mortality due to albumin substitution in HCC-free cirrhotic patients undergoing large volume paracentesis.
J Gastroenterol Hepatol 2017;32:327– 338.
[9] Simonetti RG,et al.
Plasma expanders for people with cirrhosis and large ascites treated with abdominal paracentesis.
Cochrane Database Syst Rev 2019;6:CD004039.
[10] Benmassaoud A, et al.
Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis.
Cochrane Database Syst Rev 2020;1:CD013123.
[11] Ginés P, et al.
Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites.
Results of a randomized study.
Gastroenterology 1987;93:234–241.
[12] Zhao J, et al.
Mannitolum infusion on cirrhotic patients with tense ascites treated by paracentesis.
Chin Med J 2000;113:27–30.
[13] Chinese Medical Association Hepatology Branch.
Guidelines for diagnosis and treatment of liver cirrhosis.
Journal of Clinical Hepatobiliary Diseases[J].
2019;35(11):2408-2423.
[14] Tonon M , et al.
Natural history of acute kidney disease in patients with cirrhosis.
J Hepatol 2021;74:578–583.
[15] Wong F, et al.
Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome.
N Engl J Med 2021;384:818–828.
[16] Facciorusso A, et al.
Comparative effificacy of pharmacological strategies for management of type 1 hepatorenal syndrome: a systematic review and network meta-analysis.
Lancet Gastro enterol Hepatol 2017;2:94–102 .
[17] Nanda A, et al.
Pharmacological Therapies for Hepatorenal Syndrome: A System atic Review and Meta-Analysis.
J Clin Gastroenterol 2018;52:360–367.
[18] Best LM,et al.
Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: a network meta-analysis.
Cochrane Database Syst Rev 2019;9:CD013103.
[19] China L,et al.
A randomized trial of albumin infusions in hospitalized patients with cirrhosis.
N Engl J Med 2021;384:808–817.
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