Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis

PLoS One. 2016 Jun 30;11(6):e0157371. doi: 10.1371/journal.pone.0157371. eCollection 2016.

Abstract

MCP-1 (monocyte chemoattractant protein-1) is a proinflammatory cytokine involved in chemotaxis of monocytes. In several diseases, such as acute coronary syndromes and heart failure, elevated MCP-1 levels have been associated with poor outcomes. Little is known about MCP-1 in cirrhosis.

Aim: To investigate the relationship between MCP-1 and outcome in decompensated cirrhosis.

Methods: Prospective study of 218 patients discharged from hospital after an admission for complications of cirrhosis. Urine and plasma levels of MCP-1 and other urine proinflammatroy biomarkers: osteopontin(OPN), trefoil-factor3 and liver-fatty-acid-binding protein were measured at admission. Urine non-inflammatory mediators cystatin-C, β2microglobulin and albumin were measured as control biomarkers. The relationship between these biomarkers and the 3-month hospital readmission, complications of cirrhosis, and mortality were assessed.

Results: 69 patients(32%) had at least one readmission during the 3-month period of follow-up and 30 patients died(14%). Urine MCP-1 and OPN levels, were associated with 3-month probability of readmission (0.85 (0.27-2.1) and 2003 (705-4586) ug/g creat vs 0.47 (0.2-1.1) and 1188 (512-2958) ug/g creat, in patients with and without readmission, respectively; p<0.05; median (IQR)). Furthermore, urine levels of MCP-1 were significantly associated with mortality (1.01 (1-3.6) vs 0.5 (0.2-1.1) μg/g creat, in dead and alive patients at 3 months; p<0.05). Patients with higher levels of urine MCP-1 (above percentile 75th) had higher probability of development of hepatic encephalopathy, bacterial infections or AKI. Urine MCP-1 was an independent predictive factor of hospital readmission and combined end-point of readmission or dead at 3 months. Plasma levels of MCP-1 did not correlated with outcomes.

Conclusion: Urine, but not plasma, MCP-1 levels are associated with hospital readmission, development of complications of cirrhosis, and mortality. These results suggest that in cirrhosis there is an inflammatory response that is associated with poor outcomes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / urine
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / urine*
  • Fatty Acid-Binding Proteins / urine
  • Female
  • Humans
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / mortality*
  • Liver Cirrhosis / urine
  • Male
  • Middle Aged
  • Osteopontin / urine
  • Patient Discharge
  • Patient Readmission
  • Predictive Value of Tests
  • Prognosis
  • Survival Rate
  • Trefoil Factor-3 / urine
  • Young Adult

Substances

  • Biomarkers
  • Chemokine CCL2
  • Fatty Acid-Binding Proteins
  • Trefoil Factor-3
  • Osteopontin

Grants and funding

Some of the work mentioned has been supported by a grant awarded to Pere Ginès (PG) (FIS PI12/00330), from Fondos de Investigación de Salud Carlos III integrated in the Plan Nacional I+D+I and co-funded by ISCIII-Subdirección General de Evaluación and European Regional Development Fund FEDER and from Agencia de Gestió d’Ajuts Universitaris I de Recerca (AGAUR) 2014/SGR 708. PG is a recipient of an ICREA Academia Award. Isabel Graupera was supported by a grant from the Plan Estatal I+D+I and Instituto Carlos III (Rio-Hortega fellowship: CM14/00122). Cristina Solé was supported by a grant from the Instituto de Salud Carlos III (FI14/00227). Patricia Huelin was supported by a grant from the University of Barcelona (APIF2015). PG is recipient of an ICREA Academia Award. CIBEREHD is funded by the Instituto de Salud Carlos III. PG has previously received funding from Ferring Pharmaceuticals, Grifols S.A, and Sequana Medical. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.