Albumin Substitution in Decompensated Liver Cirrhosis: Don’t Forget Zinc

Decompensated liver cirrhosis has a dismal prognosis, with patients surviving on average for 2–4 years after the first diagnosis of ascites. Albumin is an important tool in the therapy of cirrhotic ascites. By virtue of its oncotic properties, it reduces the risk of cardiovascular dysfunction after paracentesis. Treatment with albumin also counteracts the development of hepatorenal syndrome and spontaneous bacterial peritonitis. More recently, the positive impact of long-term albumin supplementation in liver disease, based on its pleiotropic non-oncotic activities, has been recognized. These include transport of endo- and exogenous substances, anti-inflammatory, antioxidant and immunomodulatory activities, and stabilizing effects on the endothelium. Besides the growing recognition that effective albumin therapy requires adjustment of the plasma level to normal physiological values, the search for substances with adjuvant activities is becoming increasingly important. More than 75% of patients with decompensated liver cirrhosis do not only present with hypoalbuminemia but also with zinc deficiency. There is a close relationship between albumin and the essential trace element zinc. First and foremost, albumin is the main carrier of zinc in plasma, and is hence critical for systemic distribution of zinc. In this review, we discuss important functions of albumin in the context of metabolic, immunological, oxidative, transport, and distribution processes, alongside crucial functions and effects of zinc and their mutual dependencies. In particular, we focus on the major role of chronic inflammatory processes in pathogenesis and progression of liver cirrhosis and how albumin therapy and zinc supplementation may affect these processes.

Albumin Might Attenuate Bacteria-Induced Damage on Kupffer Cells for Patients with Chronic Liver Disease

Chronic liver diseases (CLDs) are complex diseases that cause long-term inflammation and infection, which in turn accelerate their development. The usage of albumin in patients with CLDs has been debated for years. Human serum albumin (HSA) plays a key role in immunomodulation during the process of CLDs. The correlation between albumin and C-reactive protein (CRP) in CLD patients was analyzed by linear regression with the Pearson statistic. The damage of THP-1 and primary cells was evaluated by measuring the lactate dehydrogenase (LDH) in the supernatant. Immunofluorescence staining was performed to determine underlying pathways in Kupffer cells (KCs). Albumin negatively correlated with infection in patients with CLDs. In vitro experiments with THP-1 cells and KCs showed that albumin reduced LDH release after stimulation with bacterial products, while no differences in hepatic stellate cells (HSCs) and sinusoidal endothelial cells (SECs) were detected. Moreover, immunofluorescence staining revealed an increase of p-ERK and p-NF-kB p65 density after albumin treatment of KCs stimulated by bacterial products. In conclusion, albumin could assist CLD patients in alleviating inflammation caused by bacterial products and might be beneficial to patients with CLDs by securing KCs from bacteria-induced damage, providing a compelling rationale for albumin therapy in patients with CLDs.

Evaluation of the Appropriateness of Albumin Usage in a Teaching Hospital in Iran: The Impact of Clinical Pharmacist Intervention

Background: Albumin is a colloidal protein medication in which has a limited availability in market and it has a high cost. Albumin must be used in such approved indications as, large volume paracentesis, plasmapheresis, spontaneous bacterial peritonitis and hepato-renal syndrome. Objectives: The aim of this study was to evaluate the appropriateness of albumin utilization in a teaching hospital in Iran before and after guideline implementation. Methods: In this prospective study, a total of 100 patients were enrolled into the study in Loghman Hakim Teaching Hospital. The medical records of patients were reviewed and some information such as demographic parameters, albumin indication, albumin therapy duration, appropriateness of indication, nutrition type were recorded in pre-intervention phase. Then in post-intervention phase, albumin was administered after clinical pharmacist teaching and guideline implementation. After post-intervention period, demographic parameters, albumin indication, albumin therapy duration, appropriateness of indication were recorded again. Results: In phase 1, albumin was mostly prescribed in inappropriate indications and internist physicians were the most physicians who ordered albumin and wound healing also was the most frequent indication for albumin therapy. This improvement also was significant (P < 0.05). Data showed that albumin indication in post-intervention was different from that in the pre-intervention phase. After clinical pharmacist intervention most of indications were appropriately. Conclusions: This study demonstrated that in this hospital, albumin was prescribed inappropriately in most cases based on hospital guideline. This rate improved after clinical pharmacist intervention and resulted in significant reduction in albumin irrational utilization. It is advisable that albumin prescription must be monitored carefully by clinical pharmacists.

Effect of albumin on indicators of systemic inflammation and endothelial dysfunction in patients with alcoholic liver cirrhosis in combination with obesity

The aim of the study was to study the effect of albumin on the indicators of systemic inflammation and endothelial dysfunction in patients with ACL in combination with obesity. Material and Methods. The study included 52 patients with ACL in combination with obesity (confirmed before the onset of ascites) with the first-onset uncomplicated ascites of grade 2-3, 46 men and 6 women aged 35 to 59 years; 32 patients were diagnosed with Child-Pugh score of class B, and 20 with Child-Pugh score of class C. Depending on the treatment, the patients were divided into 2 groups: Group I included 26 patients who received albumin 40.0 g/week in combination therapy for 2 weeks of inpatient treatment, and 20.0 g/week for 12 weeks of outpatient treatment, followed by a maintenance dose of 20.0 g/month (10.0 g/2 weeks) for 12 weeks; Group II included 26 patients who received basic therapy without albumin. The control group was comprised of 20 virtually healthy donors. The patients' condition, indicators of systemic inflammation and endothelial dysfunction were assessed before treatment, 12 and 24 weeks after the treatment onset. Results and Discussion. Within 24 weeks, all patients in both groups remained alive. In obese patients with ACL, the inclusion in the complex therapy of long-term use of albumin helps to improve the course of the disease according to the Child-Pugh score. The use of albumin in the complex treatment of patients with ACL in combination with obesity during 12 weeks helps to reduce the systemic inflammatory process in terms of hs-CRP and TNFa and to reduce endothelial dysfunction in terms of ADMA and IAP-1. The use of maintenance albumin therapy helps to stabilize the process with a tendency for further reduction of the indicators of CRP, TNFa, ADMA and IAP-1. Increased systemic inflammation and endothelial dysfunction are reported in patients who did not receive long-term albumin therapy. Conclusions. The use of albumin at a dose of 20.0 g/week during 12 weeks of outpatient treatment helps to improve the course of ALC in combination with obesity according to the Child-Pugh score, along with a decrease in systemic inflammation and endothelial dysfunction. The use of maintenance therapy with albumin of 20.0 g/month during 12 weeks helps to stabilize the patient's condition with a tendency to further reduction of the incidence of systemic inflammation and endothelial dysfunction. Key words: alcoholic liver disease; liver cirrhosis; obesity; inflammation; endothelial dysfunction

Effectiveness of intravenous albumin therapy to prevent spontaneous bacterial peritonitis, renal dysfunction and death in adults with cirrhosis: a protocol for a systematic review

IntroductionUse of albumin therapy is recommended for management of disease complications in cirrhosis. The effectiveness of albumin to prevent specific disease complications and death, however, is less clear.Methods and analysisWe will search Medline (Ovid), Embase (Ovid), Cochrane Hepato-Biliary Controlled Trials Register and Cochrane Central Register of Controlled Trials for published reports on randomised controlled trials and observational studies on the effectiveness of intravenous albumin therapy to prevent spontaneous bacterial peritonitis, renal dysfunction and death in cirrhotic patients. Two independent reviewers will screen the studies for eligibility, extract data and assess risk of bias and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation system. Random effects meta-analyses will be performed when appropriate.Ethics and disseminationAs no primary data will be collected, a formal ethical approval is not required. We plan to publish the results of this study in a relevant peer-reviewed journal or journals. The study results may also be presented at relevant conferences and meetings.PROSPERO registration numberCRD42018100798.