Organ dysfunction in cirrhosis: a mechanism involving the microcirculation

Abstract

Introduction Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. Patients and methods We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan–Meier analysis was carried out. Results Fifty-four patients and 18 controls were included. Inflammatory and endothelial markers increased in advanced disease. FCD was reduced and RBCA was progressively lower according to disease severity. RBCA correlated inversely with inflammatory and endothelial biomarkers, and directly with renal function. The presence of hepatic encephalopathy correlated inversely with RBCA and directly with IL-6 and endothelin-1. In multivariate analysis, RBCA was an independent factor for organ dysfunction. The area under the receiver operating chartacteristic curve for IL-6 for survival was 0.74 (0.59–0.89), P=0.05. Transplant-free survival was 97.5% for values under 5.78 ng/ml (IL-6 best cutoff) and 83.9% above 5.78 ng/ml, log-rank=0.018. Eleven patients underwent transplantation, with an overall improvement in microcirculatory function. Conclusion Our results suggest a mechanism of organ damage in cirrhosis, where microcirculatory dysfunction could be correlated to inflammatory and endothelial biomarkers, and loss of multiorgan function. IL-6 seems to be an important survival marker of inflammation. Liver transplantation improved microcirculatory dysfunction, corroborating this hypothesis.

Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction

“…62,63 Likewise, a link between altered microcirculation, severity of cirrhosis and organ failure was also reported for patients with decompensated cirrhosis. 64 Molecular mechanisms that promote and aggravate cardiovascular dysfunction As previously discussed, PH plays a pivotal role in the development of cardiovascular dysfunction in cirrhosis. Furthermore, the pro-inflammatory and pro-oxidant milieu of decompensated cirrhosis are now considered a major cause of diffuse endothelial activation and microvascular dysfunction, which are the background for arterial vasodilation, multi-organ dysfunction and failure.…”

Portal vein thrombosis and renal dysfunction: a national comparative study of liver transplant recipients for NAFLD versus alcoholic cirrhosis

“…Multiple factors contribute to the development of PVT and RD in cirrhotic patients [ 3 , 8 ]. Cirrhosis leads to an imbalance between anti‐thrombotic factors (e.g., antithrombin III and proteins C and S) [ 9 , 10 ], and pro‐thrombotic and pro‐inflammatory mediators that predispose to the development of venous thrombosis [ 11 , 12 ], especially where the blood flow is reduced such as in the portal system from the increased resistance of the intrahepatic vascular bed [ 8 , 13 ]. The additional presence of hypotension from systemic vasodilation [ 14 , 15 ] and intravascular contraction from the formation of ascites [ 14 ] activate the angiotensin‐aldosterone cascade [ 14 ] with subsequent arterial vasoconstriction and drop in the glomerular filtration rate [ 7 , 11 , 12 ].…”

Clinical and capillaroscopic findings in patients with liver disease and proximal apparent leukonychia (Terry nails and its variants)

“…[ 26 ] Red blood cell acceleration and functional capillary density on capillaroscopy in patients with liver cirrhosis were lower than that of controls in a study. [ 30 ] We found significant alterations in patients with liver cirrhosis, particularly dilatations of the venous loop and prominence of the venous plexus. These alterations have not received much attention in the literature, although they could be similar to those described by Pirovino et al at the beginnings of capillaroscopy.…”