Open Access Open Badges Research article

Treatment of acute pancreatitis with protease inhibitors administered through intravenous infusion: an updated systematic review and meta-analysis

Takeshi Seta14, Yoshinori Noguchi2, Satoru Shikata3 and Takeo Nakayama4*

Author Affiliations

1 Division of Gastroenterology and Hepatology, Japanese Red Cross Society Wakayama Medical Center, 4-20, Komatsubara-dori, Wakayama, Wakayama 640-8558, Japan

2 Division of General Internal Medicine, Japanese Red Cross Society Nagoya Daini Red Cross Hospital, Myoken-cho 2-9, Showa-ku, Nagoya-city 466-8650, Aichi, Japan

3 Department of Family medicine, Mie Prefectural Ichishi Hospital, 616 Minami ieshiro, Hakusan-cho, Tsu-city, Mie 515-3133, Japan

4 Department of Health Informatics, Kyoto University School of Public Health, Yoshida-Konoe, Sakyo-ku, Kyoto, Kyoto 606-8501, Japan

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BMC Gastroenterology 2014, 14:102  doi:10.1186/1471-230X-14-102

Published: 30 May 2014



The intravenous use of protease inhibitors in patients with acute pancreatitis is still controversial. The purpose of this study was to evaluate the effectiveness of protease inhibitors intravenously administered to prevent pancreatitis-associated complications.


We updated our previous meta-analysis with articles of randomized controlled trials published from January 1965 to March 2013 on the effectiveness of protease inhibitors for acute pancreatitis. A systematic search of PubMed, EMBASE, the Cochrane Library, and Japana Centra Revuo Medicina was conducted. In addition, Internet-based registries (,, UMIN, JMACCT, and JAPIC) were used to search for on-going clinical trials. Furthermore, references of review articles and previously published meta-analyses were handsearched. The main outcome of interest was the overall mortality rate from acute pancreatitis.


Seventeen trials were selected for analysis. Overall, protease inhibitors did not achieve a significant risk reduction in mortality (pooled risk difference [RD], -0.02; 95% Confidence Interval [CI], -0.05 to 0.01; number needed to treat [NNT], 74.8) with low heterogeneity. A subgroup analysis in moderate to severe pancreatitis (defined by control mortality rate [CMR] >0.10) did not show a significant effect of protease inhibitors to prevent death (pooled RD, -0.03; 95% CI, -0.07 to 0.01; NNT, 1603.9) with low heterogeneity. An additional subgroup analysis of two trials with CMR >0.20 (i.e., low quality) revealed a significant risk reduction.


The present meta-analysis re-confirmed that there is no solid evidence that supports the intravenous use of protease inhibitors to prevent death due to acute pancreatitis.

Acute pancreatitis; Protease inhibitors; Mortality; Control mortality rate; Complication