Posttranscriptional changes of serum albumin: clinical and prognostic meaning in hospitalized patients with cirrhosis.

Background & Aims. Beside the regulation of fluid distribution, human serum albumin (HSA) carries other activities, such as binding, transport and detoxification of many molecules. In patients with cirrhosis, HSA presents post-transcriptional alterations which likely affect its functions. This study aimed at identifying the structural HSA alterations occurring in cirrhosis and determining their relationship with specific clinical complications and patient survival. Methods. 168 patients with cirrhosis, 35 with stable conditions and 133 hospitalized for acute clinical complications, and 94 healthy controls were enrolled. Post-transcriptional HSA molecular changes were identified and quantified by using a HPLC-ESI-MS technique. Clinical and biochemical parameters were also recorded and hospitalized patients were followed up to one year. Results. Seven HSA isoforms carrying one or more post-transcriptional changes were identified. Altered HSA isoforms were significantly more represented in patients than in healthy controls. Conversely, the native, unchanged HSA isoform was significantly reduced in cirrhosis. Native HSA and most altered isoforms correlated with both Child-Pugh and MELD scores. In hospitalized patients, oxidized and N-terminal truncated isoforms were independently associated to ascites, renal impairment, and bacterial infection. Finally, the native HAS and cysteinilated/N-terminal truncated isoforms were predictors of 1-year survival, with greater prognostic accuracy than total serum albumin concentration. Conclusions. Extensive post-transcriptional changes of HSA, involving several molecular sites and increasing in parallel with disease severity, occur in patients with cirrhosis. Altered isoforms are independently associated with specific clinical complications, while the residual, native HSA isoform independently predicts patient survival, supporting the concept of the “effective albumin concentration", which implies that the global HSA function is related not only to its serum concentration, but also to the preservation of its structural integrity.