Publication

Abstract : We read with great interest the landmark study published by Casulleras et al., entitled "Albumin internalizes and inhibits endosomal TLR signaling in leukocytes from patients with decompensated cirrhosis". 1 The study eloquently illustrates the hitherto inadequately characterized but much needed molecular and "-omics" level understanding of the immunomodulatory effects of albumin. The authors must be congratulated for their well-designed and impeccably carried out trial that takes the bench to the bedside. We would like to put forth a few observations from a clinician's perspective. Previous studies had divergent and often conflicting results regarding the efficacy of human serum albumin(HSA) in the treatment of decompensated cirrhosis, who have limited alternatives to liver transplantation. This is quite expected due to the heterogeneity of study population, dosage and frequency of albumin, presence of acute-on-chronic liver failure and other co-morbidities including renal dysfunction and effects of supportive therapies. Some results need further explanation as in the recently published literature 2,3 the effects on composite end-points were seen only in patients receiving high dose albumin, but the present study shows beneficial effects even with sub-therapeutic doses. More recent studies 4 have argued the case for near normalization of serum albumin as a predictor for improved survival and decreased incidence of infective complications. This may be important clinically as fluid overloaded patients are often precluded from the beneficial effects of albumin administration due to fear of pulmonary edema and cardiac dysfunction. Secondly, it is intriguing why plasma CpG DNA levels did not decrease significantly after treatment even though the downstream effector mediators decreased significantly across all groups. Also, of note, it is well known that albumin can inhibit TNF expression via direct down regulation of transcription pathways and indirectly via glutathione preservation, leading to down regulation of signaling via NF-kB pathway. 5,6 However, in this study this could not be observed and there was no significant reduction in TNF-α levels after albumin