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.
Highlights
Increasing evidence suggest that there is a chronic inflammatory reaction in cirrhosis that may play a role in determining patients outcome[1, 2]
Our results show that urine but not plasma monocyte chemoattractant protein-1 (MCP-1) levels are associated with hospital readmission, development of complications and poor survival in patients with decompensated cirrhosis
The main finding of the current study is that urine MCP-1 levels are associated with hospital readmission and mortality within 3-months
Summary
Increasing evidence suggest that there is a chronic inflammatory reaction in cirrhosis that may play a role in determining patients outcome[1, 2]. This can be an aseptic inflammation, at least in some patients, not related to the presence of detectable infections[3].Several lines of evidence support this hypothesis. To gain a further insight in this hypothesis of presence and relevance of systemic inflammation in cirrhosis, we studied monocyte chemoattractant protein-1 (MCP-1) levels in a prospective study in a large series of patients with cirrhosis. The inhibition of MCP-1 has been shown to ameliorate a variety of inflammatory renal diseases, including diabetic nephropathy [16]
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