Circulating cytokines in predicting development of severe acute pancreatitis

Abstract

Introduction: Severe acute pancreatitis (AP) is associated with high morbidity and mortality. Early prediction of severe AP is needed to improve patient outcomes. The aim of the present study was to find novel cytokines or combinations of cytokines that can be used for the early identification of patients with AP at risk for severe disease.

Methods: We performed a prospective study of 163 nonconsecutive patients with AP, of whom 25 had severe AP according to the revised Atlanta criteria. Admission serum levels of 48 cytokines and growth factors were determined using Bio-Plex Pro Human Cytokine Assay 21-plex and 27-plex magnetic bead suspension panels. Admission plasma levels of C-reactive protein (CRP), creatinine and calcium were measured for comparison. In subgroup analyses, we assessed the cytokine profiles of patients with severe AP (n = 14) who did not have organ dysfunction (OD) upon admission (modified Marshall score <2).

Results: Of 14 cytokines elevated in the severe AP group, interleukin 6 (IL-6) and hepatocyte growth factor (HGF) levels were independent prognostic markers of severe AP. IL-6, HGF and a combination of them predicted severe AP with sensitivities of 56.0%, 60.0% and 72.0%, respectively, and specificities of 90.6%, 92.8% and 89.9%, respectively. The corresponding positive likelihood ratio (LR+) values were 5.9, 8.3 and 7.1, respectively. The predictive values of CRP, creatinine and calcium were comparable to those of the cytokines. In subgroup analyses of patients with severe AP and without OD upon admission, we found that IL-8, HGF and granulocyte colony-stimulating factor (G-CSF) levels predicted the development of severe AP, with G-CSF being the most accurate cytokine at a sensitivity of 35.7%, a specificity of 96.1% and a LR+ of 9.1.

Conclusions: IL-6 and HGF levels upon admission have prognostic value for severe AP which is similar to levels of CRP, creatinine and calcium. Although IL-6 and HGF, as either single or combined markers, were not perfect in identifying patients at risk for severe AP, the possibility that combining them with novel prognostic markers other than cytokines might improve prognostic accuracy needs to be studied. The accuracy of IL-8, HGF and G-CSF levels in predicting severe AP in patients without clinical signs of OD upon admission warrants larger studies.

Figures

Figure 1

Patient classifications according to modified Marshall score [[20]] and revised Atlanta criteria [[1]] upon admission. MMS, Modified Marshall score.

Figure 2

Receiver operating characteristic curves of C-reactive protein and interleukin 6 plus hepatocyte growth factor for prediction of severe acute pancreatitis in the entire acute pancreatitis patient cohort (N = 163). Boxes indicate clinically optimal cutoff points used to calculate the sensitivity and specificity of each biomarker listed in Table 5. CRP, C-reactive protein; HGF, Hepatocyte growth factor; IL, Interleukin.

Figure 3

Receiver operating characteristic curves of granulocyte colony-stimulating factor and C-reactive protein for prediction of severe acute pancreatitis in patients with admission modified Marshall scores <2 (N = 142). Boxes indicate clinically optimal cutoff points used to calculate the sensitivity and specificity of each biomarker given in Table 7. CRP, C-reactive protein; G-CSF, Granulocyte colony-stimulating factor; MMS, Modified Marshall score.