Circulating mannan-binding lectin, M-, L-, H-ficolin and collectin-liver-1 levels in patients with acute liver failure

Abstract

Background & aims: The complement system is activated in liver diseases including acute liver failure (ALF); however, the role of the lectin pathway of complement has scarcely been investigated in ALF. The pathway is initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL), M-, L-, and H-ficolin and collectin-liver-1 (CL-L1), which are predominantly synthesized in the liver. We aimed to study lectin levels in ALF patients and associations with clinical outcome.

Methods: Serum samples from 75 patients enrolled by the US ALF Study Group were collected on days 1 and 3. We included 75 healthy blood donors and 20 cirrhosis patients as controls. Analyses were performed using sandwich-type immunoassays (ELISA, TRIFMA).

Results: At day 1, the MBL level in ALF patients was 40% lower compared with healthy controls {[median (interquartile range) 0.72 μg/ml(0.91) vs. 1.15 (1.92)(P = 0.02]}, and increased significantly by day 3 [0.83 μg/ml(0.94)(P = 0.01)]. The M-ficolin level was 60% lower [0.54 μg/ml(0.50) vs. 1.48(1.01)(P < 0.0001)]. The CL-L1 level at day 1 was slightly higher compared with healthy controls [3.20 μg/ml(2.37) vs. 2.64(0.72)(P = 0.11)]; this was significant at day 3 [3.35(1.84)(P = 0.006)]. H- and L-ficolin levels were similar to healthy controls. Spontaneous ALF survivors had higher levels of MBL at day 1 [0.96 μg/ml(1.15) vs. 0.60(0.60)(P = 0.02)] and lower levels of L-ficolin by day 3 compared with patients who died or were transplanted [1.61 μg/ml(1.19) vs. 2.17(2.19)(P = 0.02)].

Conclusion: We observed significant dynamics in lectin levels in ALF patients, which may suggest they play a role in ALF pathogenesis. High MBL and low L-ficolin levels are associated with survival.

Keywords: acute liver failure; collectin-liver-1; complement system; ficolins; mannan-binding lectin; the lectin pathway.

Figure 1

Collectin and ficolin levels ((a) MBL, (b) M-ficolin, (c) L-ficolin), (d) H-ficolin, (e) CL-L1) in patients with acute liver failure on day 1 and 3 of enrolment, patients with stable alcoholic cirrhosis and healthy blood donors. The box plots represent median and 25–75 percentiles. Upper and lower lines are the upper and lower adjacent values.

Figure 1

Collectin and ficolin levels ((a) MBL, (b) M-ficolin, (c) L-ficolin), (d) H-ficolin, (e) CL-L1) in patients with acute liver failure on day 1 and 3 of enrolment, patients with stable alcoholic cirrhosis and healthy blood donors. The box plots represent median and 25–75 percentiles. Upper and lower lines are the upper and lower adjacent values.

Figure 1

Collectin and ficolin levels ((a) MBL, (b) M-ficolin, (c) L-ficolin), (d) H-ficolin, (e) CL-L1) in patients with acute liver failure on day 1 and 3 of enrolment, patients with stable alcoholic cirrhosis and healthy blood donors. The box plots represent median and 25–75 percentiles. Upper and lower lines are the upper and lower adjacent values.

Figure 1

Collectin and ficolin levels ((a) MBL, (b) M-ficolin, (c) L-ficolin), (d) H-ficolin, (e) CL-L1) in patients with acute liver failure on day 1 and 3 of enrolment, patients with stable alcoholic cirrhosis and healthy blood donors. The box plots represent median and 25–75 percentiles. Upper and lower lines are the upper and lower adjacent values.

Figure 1

Collectin and ficolin levels ((a) MBL, (b) M-ficolin, (c) L-ficolin), (d) H-ficolin, (e) CL-L1) in patients with acute liver failure on day 1 and 3 of enrolment, patients with stable alcoholic cirrhosis and healthy blood donors. The box plots represent median and 25–75 percentiles. Upper and lower lines are the upper and lower adjacent values.

Figure 2

(a) MBL levels in patients with acute liver failure at day 1 and 3 in relation to survival status. (b) L-ficolin levels in patients with acute liver failure in relation to survival status (Spont Surv, patients with spontaneous survival; Dead, patients who underwent liver transplantation or died without transplantation).

Figure 2

(a) MBL levels in patients with acute liver failure at day 1 and 3 in relation to survival status. (b) L-ficolin levels in patients with acute liver failure in relation to survival status (Spont Surv, patients with spontaneous survival; Dead, patients who underwent liver transplantation or died without transplantation).

Figure 3

Levels of CL-L1 at day 1 and day 3 in patients with acute liver failure according to aetiology (Acetamin, acetaminophen; Drug Hep, drug hepatitis; Viral Hep, viral hepatitis, Indeterm, indeterminate) compared to healthy controls. (*, p<0.03 when compared with non-acetaminophen cases; x, p=0.0002 when compared with healthy controls).