Elsevier

The Lancet

Volume 355, Issue 9219, 3 June 2000, Pages 1955-1960
The Lancet

Articles
Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study

https://doi.org/10.1016/S0140-6736(00)02327-8Get rights and content

Summary

Background

There is a pressing clinical requirement for an early simple test of severity in acute pancreatitis. We investigated the use of an assay of trypsinogen activation peptide (TAP).

Methods

We undertook a multicentre study in 246 patients (172 with acute pancreatitis [35 with severe disease], 74 controls). We assessed the predictive value of urinary TAP concentrations measured by a validated competitive immunoassay. We compared the results with those for plasma C-reactive protein and three clinicobiochemical scoring systems. TAP and C-reactive protein concentrations were analysed at set times after symptom onset and compared with the clinicobiochemical systems scores at key times during hospital stay.

Findings

At 24 h after symptom onset, the median urinary TAP concentration was 37 nmol/L (IQR 17–110) for severe and 15 nmol/L (5–35) for mild disease (p < 0·001). The respective values for plasma C-reactive protein were 24 mg/L (3–34) and 25 mg/L (6–75; p=0·208). The sensitivity, specificity, positive predictive, and negative predictive values of the test to show severe acute pancreatitis compared with mild acute pancreatitis at 24 h were: for TAP (>35 nmol/L), 58%, 73%, 39%, and 86%, respectively, and for C-reactive protein (>150 mg/L), 0%, 90%, 0%, and 75%. 48 h after admission the values for the clinicobiochemical scoring systems were: APACHE II (≥8), 56%, 64%, 30%, and 85%; Ranson score (≥3), 89%, 64%, 38%, and 96%; and Glasgow score (≥3), 77%, 75%, 44%, and 93%. At 48 h, the values for C-reactive protein were 86%, 61%, 37%, and 94% and for TAP were 83%, 72%, 44%, and 94%. Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy.

Interpretation

Urinary TAP provided accurate severity prediction 24 h after onset of symptoms. This single marker of severity in acute pancreatitis deserves routine clinical application.

Introduction

Acute pancreatitis affects around 40 per 100 000 of the general population, and 20–30% of attacks are severe, with a mortality of about 30–50%.1 Improved outcome is based on early recognition of disease severity to allow high-dependency or intensive treatment2 and, in the case of gallstone-linked disease, emergency endoscopic sphincterotomy.3, 4 About 50% of deaths occur within 1 week of the attack, mostly from multiorgan dysfunction syndrome.5

It is hard to identify severe cases within 2–3 days of symptom onset, by which time the network of pathophysiological mechanisms leading to multiorgan dysfunction syndrome is established. An ideal prognostic system would be based on a single test and have a high negative predictive value. To date, few prospective studies have analysed prognostic markers or systems from the time of symptom onset, which undermines their value. The APACHE II,6 Ranson,7 and Imrie8 clinicobiochemical systems have similar accuracy 48 h after hospital admission but, although used in randomised controlled trials, are not used routinely in most hospitals because they are complex.9 Only the APACHE II score has useful accuracy on admission, but it is the most complicated system.6 Single markers are not used routinely because they are useful only at 48 h or more after onset of symptoms, have not been rigorously tested or had initial reports confirmed, or laboratory measurement is difficult.10, 11, 12, 13, 14, 15

Measurement of trypsinogen activation peptide (TAP), released on activation of trypsinogen to trypsin, has promising predictive value since it is a single marker specifically related to the onset of acute pancreatitis.13 Accurate measurement of TAP has been difficult because of unavailability of a validated assay. We investigated, in a prospective multicentre study, the predictive value of a TAP assay compared with C-reactive protein10 and clinicobiochemical scoring systems.

Section snippets

Study population

Consecutive patients were recruited for 6–12 months from July, 1997, to July, 1998, at the Royal Liverpool University Hospital, Liverpool, UK, Helsinki University Central Hospital, Helsinki, Finland, Ulm University Hospital, Ulm, Germany, and the Mater Misericordiae Hospital, Dublin, Ireland. The time of onset of acute abdominal pain was determined prospectively. Eligible patients were those admitted from the community with a diagnosis of acute pancreatitis. We excluded patients who had had

Results

303 individuals were enrolled, of whom 57 were excluded because they did not meet all the eligibility criteria. 246 eligible patients were included, of whom 172 had acute pancreatitis and 74 were controls. 35 (20%) patients with acute pancreatitis had severe disease (Atlanta classification16). Sex, age, admission delay, and duration of hospital stay in relation to clinical severity and cause of acute pancreatitis are shown in table 1. Median admission delay for patients with acute pancreatitis

Discussion

Measurement of urinary TAP proved a valuable early marker of severity in acute pancreatitis, with advantages over all other available prognostic systems.6, 7, 8, 10, 11, 12, 13, 14 The use of TAP measurement for severity assessment is appealing, since activation of trysinogen to trypsin, leading to the release of TAP, precedes all other systemic and clinical events in severe acute pancreatitis.13, 20 Optimum supportive care with limited health-care resources,1, 2 as well as the application of

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