The Contribution of Serum Complement Component 3 Levels to 90-Day Mortality in Living Donor Liver Transplantation

Abstract

The contributions of the complement system have been elucidated in the process of solid organ transplantation, including kidney transplantation. However, the role of complement in liver transplantation is unknown. We sought to elucidate the time-dependent changes of peritransplantational serum complement levels and the relationships with posttransplant outcomes and other immunological biomarkers. We enrolled 82 patients who underwent living-related donor liver transplantation (LDLT). Nine patients (11%) died within 90 days after LDLT (non-survivors). The following immunomarkers were collected preoperatively and at 1, 2, and 4 week(s) after LDLT: serum C3, C4, immunoglobulin G (IgG), and peripheral blood leukocyte populations characterized by CD3, CD4, CD8, CD16, CD19, CD20, CD22, and CD56. Consequently, C3 and C4 increased time-dependently after LDLT. Preoperatively, C3 was negatively correlated with the MELD score, Child–Pugh score, CD16-positive leukocyte percentage, and the CD56-positive leukocyte percentage. Non-survivors had lower levels of C3 at 2 weeks in comparison to survivors (median [interquartile range]: 56 [49-70] mg/dL vs. 88 [71-116] md/dL, p=0.0059). When the cutoff value of C3 at 2 weeks to distinguish non-survivors was set to 71 mg/dL, the sensitivity, specificity, and area under the ROC curve were 87.5%, 75.0%, and 0.80, respectively. A principal component analysis showed an inverse relationship between the C3 and C4 levels and the percentage of CD8-, CD16-, and CD56-positive leukocytes at 1 and 2 week(s). All non-survivors were included in the cluster that showed higher percentages of CD8-, CD16-, and CD56-positive leukocytes at 2 weeks. In conclusion, we demonstrated the relationship between complement, outcomes, and other immunomarkers in LDLT and suggested the usefulness of C3 at 2 weeks after LDLT in distinguishing the mortality.

Expansion of Double-Negative T Cells in Patients before Liver Transplantation Correlates with Post-Transplant Infections

“…Biomarkers which can predict the development of infections after LTx are of great value for the optimization of immunosuppressive therapy and prevention of infections after LTx. Complementary systems, such as measuring serum complement component 3 levels at 2 weeks after transplantation, were reported as important for predicting 90-day mortality in living donor liver transplantation [ 36 ]. Mysore has also reported that patients with the highest expression of PD-1 + Tim-3 + T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days [ 13 ].…”

The predictive value of revised diastolic dysfunction in outcomes of liver transplantation: A propensity score matching analysis

“…Given the increased risk of infectious complications, upregulation of inflammatory markers and downregulation of cnidarian complements in both the advancement of cirrhosis and development of CCM were associated with poor survival (21,(45)(46)(47). Similarly, NLR was considered an effector, along with SII and PLR, in this study.…”

The time-dependent changes in serum immunoglobulin after kidney transplantation and its association with infection

“…Each component of the complement system activates the complement cascades through intricate interactions between various soluble products and cell surface receptors and plays a crucial role against infection (8,11). C4 has a central role in the classical pathway and has shown associations with early and late allograft function (8,12). All three activation cascades -classical, alternative, and lectin pathway-converge at the level of C3 to form C5 convertase and result in the formation of the membrane attack complex (1,10,12).…”

“…C4 has a central role in the classical pathway and has shown associations with early and late allograft function (8,12). All three activation cascades -classical, alternative, and lectin pathway-converge at the level of C3 to form C5 convertase and result in the formation of the membrane attack complex (1,10,12). Decreased levels of C3 have been reported to be associated with the occurrence of infectious complications after heart and lung transplantation (7,11,13).…”

“…However, the relationship between hypocomplementemia (HCC) and infection is yet controversial (7). Some studies have even reported an association between increased levels of C3 and infections such as CMV infection (4,11,12,14).…”