Sponsored: Human albumin: Focus on liver disease - Page 7

Working hypothesis of organ failure mechanism in ACLF
Liver cirrhosis
Bacterial infections PAMPs translocation
PAMPs in body fluids
Virulence pathogenic factor
Pattern recognition receptor recognition
Functional feature recognition
Severe systemic inflammatory response : cytokine storm , leukocytosis
Increased energy demand of immune cells
Competition between immune cells and non-immune cells for energy / nutrients
Immunopathology hypothesis
Immune tissue injury
Organ failure
Metabolic resource competition hypothesis
Non-immune tissues adapt by decreasing their energetic demand and reducing mitochondrial oxidative phosphorylation
and induce inflammation , 17 which can reduce inflammatory factors ( IL-6 , granulocyte colonystimulating factor , IL-1ra and vascular endothelial growth factor ) in patients with decompensated cirrhosis . 16
Structure and function of albumin The pro-inflammatory and pro-oxidative microenvironment in patients with liver cirrhosis threatens the structural integrity of the albumin molecule . The oxidative damage to the free sulfhydryl group on the Cys-34 residue is the most common change . Oxidised albumin includes two types : human non-mercaptoalbumin 1 ( HNA1 ) and human non-mercaptoalbumin 2 ( HNA2 ). HNA1 can act on peripheral blood mononuclear cells to generate a cytokine storm . 13 Other changes include post-transcriptional damage such as truncation , glycosylation and dimerisation of N- and C-terminal partial residues . After the structure of albumin is damaged , its abilities of binding , detoxification , antioxidation and chelating metal ions decreases with the severity of the disease . Therefore , the biological function of albumin and the assumption of its circulating amount and structural integrity led to the concept of an ‘ effective albumin concentration ’, which relates not only to the measurement of albumin concentration , but also for determination of function . 14 In fact , the effective albumin concentration has an independent correlation with the severity of decompensated cirrhosis and albumin function and is an effective indicator for predicting ACLF and short-term mortality . On this basis , whether the clinical treatment target can be represented by the increase in the effective albumin concentration should be explored , and new biomarkers identified .
Long-term efficacy of albumin Reducing the incidence of complications , improving patients ’ prognoses and quality of life , and reducing medical costs are important issues in the clinical diagnosis and treatment of liver cirrhosis , and longterm albumin therapy certainly has potential . In the ANSWER study , compared with standard medical treatment ( SMT ) or SMT plus albumin treatment , the 18-month survival of patients with cirrhosis and ascites in the albumin group was significantly higher ( 77 %) than that in the SMT group ( 66 %), and the risk of death was reduced by 38 %. 15 In another study , the 24-month mortality in the SMT plus albumin treatment group was also significantly lower than that in the SMT monotherapy treatment group . 16 In the MACHT study , there was no significant difference in the incidence of complications or 1-year mortality during follow-up between SMT plus albumin and midodrine hydrochloride treatment or SMT plus placebo . 17 The dose of albumin may be crucial to its function ; only high-dose albumin ( 1.5g / kg / week ) improved the effective blood volume and systemic inflammation in patients with stable decompensated cirrhosis . 16
Conclusion and future prospects In the past 20 years , we have gained a more indepth understanding of the pathogenesis of
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