Value of adipokines in predicting the severity of acute pancreatitis: Comprehensive review

Table 4 Summary of the human studies on the prognostic value of adipokines

Study	Patients and methods	Results	Conclusions
Konturek et al[30]	Prospective observational study (n = 45) Diagnosis of AP based on Atlanta criteria Adipokines studied: leptin Adipokines evaluated between 48-72 h of illness onetime AP (n = 15) vs controls (n = 30)	Leptin: AP/controls- 7.5 (4.3-18.4) ng/mL/2.1 (1.0-11.8) ng/mL	Median plasma leptin levels in AP were significantly increased as compared with controls
Duarte-Rojo et al[34]	Prospective observational study (n = 52) Diagnosis of AP based on typical clinical manifestations with at least a 3-fold increase of serum amylase and/or lipase Whenever uncertainty about diagnosis existed, CT-scan was performed to confirm/rule out AP Severe AP was considered when patients developed one or more local or systemic complications according to the Atlanta classification of AP Adipokines studied: leptin Adipokines evaluated onetime during the 1 d of hospital stay MAP (n = 38) vs SAP (n = 14)	There was no statistically significant association between leptin serum levels and severity of AP There was no difference in leptin measurements between patients favorable and fatal outcomes (P = 0.34) Time of evolution from onset of pain did not alter leptin values There was a positive correlation of BMI and leptin (r = 0.476, P < 0.001) in the whole group Predicted severity by modified Ranson’s criteria correlated with Atlanta criteria (r = 0.414, P = 0.002); however, it did not correlate with leptin levels	Results do not support human leptin as a major pro-inflammatory signal involved in AP, nor as a protective and anti-inflammatory mediator It seems neither to be the link between obesity and a higher rate of complications in AP; nor a prognostic marker
Tukiainen et al[35]	Prospective observational study (n = 24) AP and SAP defined by Atlanta criteria Adipokines studied: leptin, adiponectin Adipokines evaluated on admission, on days 2-4, and on days 5-7 MAP (n = 12) vs SAP (n = 12)	In patients with SAP highest value of CRP was 349 mg/L (284-476 mg/L), with MAP 119 mg/L (11-367 mg/L) Leptin on admission SAP/MAP [6.1 (1.6-72.9) ng/L]/[9.0(2.5-36 .5) ng/L], (P > 0.05); on days 2-4, 7.7 (1.6-13.9) ng/L/3.8(1.6-12.9) ng/L, (P > 0.05) Adiponectin on admission SAP/MAP, [5642 (1201-19 400) ng/L]/[6314 (1980-24 340) ng/L], (P > 0.05)	Plasma levels of adiponectin and leptin do not correlate with AP severity on admission and during the first week of the disease
Schäffler et al[37]	Pilot prospective observational study (n = 23) Diagnosis of AP was based on clinical, laboratory and radiological findings during CT and/or ultrasound examination Adipokines studied: leptin, adiponectin, resistin Adipokines evaluated daily for 10 d after admission SAP (n = 20) vs MAP (n = 3) and patients with high points vs low points on radiological scores	Balthazar score: 4 (1-5), Schroeder score: 5 (1-7), Necrosis score: 2(1-4) Ranson: 3 (0-7), Apache II: 12 (4-37) Resistin has a significant positive correlation with Ranson score (r= 0.6, P = 0.002) and with Apache II score (r = 0.5, P = 0.019) Resistin: intervention group/no intervention, 32.4 ± 10.7 ng/L/15.8 ± 5.1 ng/L, P = 0.026 Leptin and relative changes in leptin values were positively and significantly correlated with CRP levels (r = 0.6, P = 0.007 and P = 0.003, respectively) Resistin cut-off value of > 9.2 ng/mL (10 d mean value) can provide a PPV of 91.9% in predicting Schroder score of > 3 (specificity 85%, sensitivity 75%, AUC 0.9, P < 0.0001) Leptin cut-off value of 15.0 ng/mL can provide a PPV of 88% in predicting Schroder score of > 3 (specificity 85%, sensitivity 50%, AUC 0.72, P < 0.0001) Day 1 resistin proved to predict a Schroder score > 3 with a PPV of 93.3%, cut-off 6.95 ng/mL, specificity 87.5%, sensitivity 93.3%; AUC 0.9, P = 0.002)	Serum adipokines might be the new useful early markers of disease severity in AP
Leśniowski et al[33]	Prospective observational study (n = 79) All AP was classified as grade B according to Balthazar CT score Adipokines studied: adiponectin, resistin Adipokines evaluated onetime during the first day of hospitalization AP (n = 39) vs controls (n = 40)	Resistin: AP/controls, 8.38 ± 4.87 ng/mL/3.58 ± 1.51 ng/mL, P < 0.05 Adiponectin: AP/controls, 119.38 ± 61.75 ng/mL/133.77 ± 55.38 ng/mL, P > 0.05 CRP: AP/controls, 23.21 ± 8.75 ng/mL/3.95 ± 1.06 mg/L, P < 0.01 Weak positive correlation between serum resistin and CRP was observed (r = 0.57, P < 0.05) No correlation between selected adipocytokines and BMI was noticed	Serum concentrations of resistin may possibly represent the useful early marker of inflammatory response in AP
Sharma et al[36]	Prospective observational study (n = 60) Diagnosis of AP based on Atlanta criteria SAP was defined as the presence of cardiovascular, pulmonary, and/or renal system dysfunction during the initial hospital admission during for at least 48 h Adipokines studied: adiponectin Adipokines evaluated on admission and subsequently up to 30th hospital day MAP (n = 27) vs SAP (n = 33)	Serum adiponectin levels from days 1 to 3 were significantly lower for patients with SAP [median 3.74 (0.83-8.92) μg/L] than those with MAP [6.58 (1.31-15.37) μg/L], P = 0.02 Serum adiponectin levels from days 4 to 7 were lower for patients with SAP [median 4.53 (0.94-18.2) μg/L] than those with MAP [8.06 (2.11-17.72) μg/L], P = 0.01 1-3 d serum adiponectin threshold of 4.5 μg/mL correctly classified the severity of 81% of patients with AP This threshold yielded a sensitivity of 70%, specificity 85%, PPV 64%, NPV 88%, AUC 0.75	Serum adiponectin levels are significantly lower in patients with SAP than those with MAP and could serve as inverse marker of systemic inflammatory response to pancreatic injury
Daniel et al[40]	Prospective observational study (n = 62) Diagnosis of AP was based on at least threefold elevated serum amylase level, as well as ultrasonography and CT In all cases AP was classified as C according to Balthazar’s CT score and as severe according to Ranson’s criteria (3 points) Adipokines studied: resistin Adipokines evaluated on 1, 2, 3 and 5 d of hospitalization SAP (n = 32) vs controls (n = 30)	On first day of observation , the median serum CRP level was 51.9 ± 46.1 mg/L, significantly higher than in control group (3.44 ± 3.04 mg/L, P = 0.01), and further increased at third day of hospitalization (102.6 ± 55.1 mg/L, P < 0.05), slightly decreasing on fifth day of hospitalization (78 ± 47.7 mg/L) The values observed at third and fifth day of hospitalization were significantly higher than in the control group (P < 0.001) One day of admission and third day of the hospitalization the mean serum resistin concentration was 12.9 ± 6.38 ng/mL and 17.4 ± 4.23 ng/mL, respectively Both values were significantly higher than in the control group (4.06 ± 2.63 ng/mL, P < 0.05) At fifth day of hospitalization serum resistin concentration increase further to 25.8 ± 8.14 ng/mL, which was significantly higher than at first and third day (P < 0.05) of hospital stay Significant correlation between CRP and resistin (r = 0.43, P < 0.05) during the hospital stay was found	Resistin may be useful early marker in edematous form of AP
Schäffler et al[38,39]	Prospective observational study (n = 50) Diagnosis of AP was based on clinical, laboratory and radiological findings during CT and/or ultrasound examination All patients were divided into three groups: first - with higher radiological score’s points, second - with lower radiological score’s points and third - no CT scan (mild pancreatitis) Adipokines studied: leptin, adiponectin, resistin, visfatin Adipokines were measured daily from admission till 10 d of hospital stay SAP (n = 41) vs MAP (n = 9) and patients with high points vs low points on radiological scores	Balthazar score: 4.0 (1-5), Schroeder score: 4.5 (1-7), Necrosis score: 1.5 (1-4), Ranson: 3 (0-8), Apache II: 12 (0-45) Admission resistin levels has positive an significant correlation with Apache II score (r = 6, P < 0.001) and with Ranson score (r = 0.4, P = 0.013) Admission resistin cut-off value of > 11.9 ng/mL can provide a PPV of 89% in predicting Schroeder score of > 3 (specificity 80%, sensitivity 70%, AUC 0.8, P < 0.002) Admission resistin cut-off value of > 11.9 ng/mL can serve as a positive predictor of a Balthazar score > 3 and Necrosis score > 2 Admission visfatin cut-off value of > 1.8 ng/mL can provide a PPV of 93.3% in predicting Schroeder score of > 3 (specificity 81.8%, sensitivity 93.3%, AUC 0.89, P < 0.001, likehood ratio 5.1, post-test probability 93.0%) Admission visfatin concentration can also predict Necrosis score > 2 (PPV 48.3, specificity 40.0%, sensitivity 93.8%, AUC 0.77, P < 0.004, likehood ratio 1.5, post-test probability 70.0%) and Balthazar score > 3 (PPV 79.3, specificity 57.1%, sensitivity 88.9%, AUC 0.74, P < 0.011, likehood ratio 2.1, post-test probability 55.0%)	Resistin and visfatin levels are highly elevated in patients with SAP when compared to patients with MAP Both adipokines levels are positively correlated with clinical severity, clinical end points and needs for interventions A single measurement of serum resistin or visfatin on the day of admission is a highly significant and positive predictive marker in predicting peripancreatic necrosis

AP: Acute pancreatitis; SAP: Severe acute pancreatitis; MAP: Mild acute pancreatitis; BMI: Body mass index; CRP: C-reactive protein; AUC: Area under curve; PPV: Positive predictive value; NPV: Negative predictive value; CT: Computed tomography.