Sponsored: Human albumin: Liver Disease SE Asia - Page 3

Human albumin : Focus on liver disease in South and Southeast Asia

FOREWORD
Mauro Bernardi MD Alma Mater Studiorum – Università di Bologna , Italy
Despite major advances in the management of hepatitis , the global health burden due to chronic liver disease , ultimately leading to cirrhosis and liver cancer , increases worldwide . Indeed , non-alcoholic steatohepatitis and alcoholism are progressively supplanting hepatitis virus infection as the leading cause of chronic liver disease . The refinement of tools allowing early , non-invasive diagnosis of liver fibrosis and cirrhosis is highly relevant , as early diagnosis would optimise the efficacy of available treatments . Similarly , diagnosis and treatment of liver cancer in its early stages would contribute to saving lives and prolonging patient survival .
Most chapters of this educational handbook are devoted to the use of human albumin in cirrhosis . Since its appearance on the battlefields of the Second World War , most physicians consider human albumin an excellent plasma volume expander . Furthermore , the beneficial effects following human albumin infusion are mainly attributed to this property .
The use of human albumin in liver disease is widespread and relies on a solid scientific background . As in other fields of medicine , the current , well-established indications for human albumin administration to patients with cirrhosis aim at improving effective plasma volume . In the light of the peripheral arterial vasodilation hypothesis , published in 1988 , paracentesis-induced circulatory dysfunction , acute kidney injury precipitated by spontaneous bacterial peritonitis , and the hepatorenal syndrome were seen as the expression of this hemodynamic disturbance . However , since then , our knowledge of the pathophysiological mechanisms underlying decompensated cirrhosis has improved substantially . Thus , even the therapeutic role of human albumin warrants reconsideration .
At present , there is clear evidence that sustained inflammation and a pro-oxidant state characterise the internal milieu of patients with decompensated cirrhosis . The extent of systemic inflammation progresses in parallel with the severity of cirrhosis , culminating in patients with acute-on-chronic liver failure . This condition derives from the systemic spread of pathogen-associated molecular patterns ( PAMPs ) due to abnormal translocation from the gut and damage-associated molecular patterns ( DAMPs ) from the diseased liver where extensive cell necrosis occurs . These molecules bind with innate recognition receptors and activate immune cells . An enhanced synthesis and release of pro-inflammatory cytokines and chemokines along with reactive oxygen and nitrogen species follows . This cascade of events contributes to the development of circulatory dysfunction and , along with it , favours the occurrence of multiorgan dysfunction and failure through mechanisms such as immunopathology and immune dysmetabolism , and oxidation .
Another topic worth mentioning is the post-transcriptional changes of the albumin molecule in patients with decompensated cirrhosis . They are due to systemic inflammation and oxidation and involve several domains hampering the non-oncotic properties of the molecule . Thus , the albumin deficit in patients with cirrhosis is not only quantitative but also functional .
In the light of these advances , the non-oncotic properties of human albumin assume a particular relevance . Indeed , albumin possesses domains wielding different functions , such as the free cysteine residue in position 34 , which exerts potent antioxidant and scavenging activities , and the amino terminal , which binds and removes highly toxic reactive metal species . Other domains bind , transport , and detoxify exogenous and endogenous substances , including PAMPs and DAMPs . Moreover , albumin protects capillary integrity , influences acid – base balance and coagulation , and has immunemodulatory functions . Recent studies in experimental and human cirrhosis have shown that albumin internalises in immune cells and modulates their responses by interacting with endosomal toll-like receptor signalling . Furthermore , the albumin molecule can protect tissues from inflammationinduced injury .
The improved knowledge of the pathophysiological background of decompensated cirrhosis opens novel therapeutic perspectives
The use of human albumin in liver disease is widespread and relies on a solid scientific background for patient management . The newly discovered pathophysiological pathways represent novel targets that mechanistic approaches can antagonise . Both realising new therapies and remodulating current treatments can help in improving patient care . The use of human albumin in patients with decompensated cirrhosis well represents a new therapeutic approach based on an ‘ old ’ treatment . Indeed , its oncotic and non-oncotic properties make human albumin a multitarget agent that could be considered a potential disease-modifying agent . The first results in support of this have already appeared . As an example , even though further experience is needed and several aspects would need refining , long-term human albumin administration to patients with
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