Albumin, COP and Endothelial Damage in Patients With ESLD Undergoing OLT
Condition: Transplant-Related Disorder
Study type: Observational

Summary: 
      To study the correlation between colloid osmotic pressure, albumin and the loss of vascular
      integrity in terms of endothelial dysfunction in patients with ESLD undergoing OLT and its
      impact on the perioperative course, as well as on morbidity and mortality.
    

Detailed description: 
      Patients suffering from end-stage liver disease (ESLD) are critically ill. Still, therapeutic
      options are limited, no organ replacement procedure is available and orthotopic liver
      transplantation remains the unique therapy of choice.

      ESLD is associated with a myriad of comorbidities, and is characterized by imbalances in the
      acid-base- status, coagulopathy, metabolic disorders and activation of the pro-inflammatory
      cascade. ESLD represents a state of generalized systemic inflammation subsequently leading to
      endothelial dysfunction and capillary leak syndrome, potentially culminating in end-organ
      dysfunction.

      Furthermore, patients with ESLD suffer from reduced regenerative and synthetic
      capacity/ability, which is reflected by the serum albumin deficiency. Serum albumin is the
      most important plasma protein, is produced exclusively in the liver, and houses various
      physiological functions: it owns immunological, immuno-modulating and anti-inflammatory
      properties, transport capacities, as well as detoxifying qualities. However, the most well
      known property of human serum albumin is maintaining the colloid osmotic pressure (COP). In
      the healthy individual, serum albumin is responsible for 75% up to 80% of the COP, whereas in
      the critically ill, the percentage proportion drops down to 17%. The COP itself accounts for
      the regulation and distribution of the plasma volume and is therefore essential in
      maintaining the vascular stability and integrity. Additionally, the endothelial glycocalyx is
      necessary in the context of safeguarding the endothelial function and regulating the vascular
      permeability. The glycocalyx covers the endothelium luminally and its core component is the
      heparan sulfate proteoglycan, syndecan-1. Under various clinical conditions, like
      ischemia/reperfusion, inflammation, sepsis, shock, major surgery, hypervolemia, degradation
      to the glycocalyx may happen. These pathophysiological circumstances may lead to loss of the
      endothelial integrity and consecutively to capillary-leak syndrome causing a loss of albumin
      and fluid extravasation/shifts. Various clinical and experimental studies could show that
      global, as well as regional ischemia and the subsequent reperfusion-phase, both lead to
      glycocalyx-shedding, in terms of increased syndecan-1 plasma levels. Furthermore, a previous
      study from our study group clearly detected increased syndecan-1 plasma levels in patients
      with ESLD as surrogate parameter of glycocalyx degradation mirroring the state of chronic
      inflammation in this patient population.

      Nevertheless, a clear correlation between colloid osmotic pressure, albumin and the loss of
      vascular integrity in state of endothelial dysfunction has not been studied before in
      patients with ESLD undergoing OLT.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Patients between 18 years and 80 years suffering from Child B/C Cirhhosis, who underwent
        OLT at the Medical University of Vienna in the period between 2014 and 2016.
      
Biospecimen description: 
      serum-samples for detection of syndecan-1 concentration
    
Keywords: glycocalyx; serum albumin; orthotopic liver transplantation; colloid osmotic pressure; endothelial dysfunction