RAP still represents a challenging disease, repeated episodes of which contribute substantially to the overall disease burden by prompting repeated hospitalization, adversely impacting quality of life as well as increasing the risk of progression to chronic pancreatitis and pancreatic tumor[2, 11–14]. RAP may run a milder clinical course than an index episode[15, 16], but the fatality rate of which was significantly higher than that of patients with first-episode AP. Few reports have studied that the more frequent the onset of RAP, the more noticeable the decrease of the total pancreas volume and tail diameter, and the higher the incidence of CP [8, 18]. Therefore, the prediction of short-term recurrence of RAP is worthwhile to the early intervention and treatment of CP.
Although Some causes were a well-established risk factors for RAP[12, 18–21]. Theoretically, if the causes of acute pancreatitis existed, they could make acute pancreatitis to relapse repeatedly. In our retrospective study of patients with RAP, we found that diabetes, hyperlipemia, drinking status, ALT, GGT were involved in increased risk of RAP recurrence. Yadav et al showed that about 1/4 of patients with recurrent acute pancreatitis of known or unknown causes have underlying chronic pancreatic disease, which may invalidate treatment to remove known possible causes of acute pancreatitis . Sajith et al found that clinical features and complications were the same in the idiopathic group and those with known etiology. So, in the present study, we only found that β2-MG and CRP were independent risk factors for short-term recurrence of RAP.
Although challenging to prove in humans, the changes in the pancreas linked to increased AP susceptibility likely involve epigenetic changes, microanatomic changes, and/or immunological changes such as populating the parenchyma widespread with tissue histiocytes (eg, macrophages, dendritic cell) , excessive inflammatory reaction of the body, and changes of inflammatory mediators and cytokines.Thus, AP results in persistent changes that strongly predisposes to RAP.β2-MG is a low molecular weight protein that is synthesized by all human nucleated cells and platelets; It is indirectly involved in the regulation of the immune system response. Some authors have found that serum β2-MG levels are elevated in patients with chronic pancreatitis[26–28],RAP is the most important risk factor for progression to end-stage CP[7, 14]. Recurrent episodes of acute pancreatitis may complicate the course of chronic subclinical pancreatitis, meaning they are the clinical expression of chronic pancreatitis diagnosed in an early phase, or otherwise they may themselves induce chronic lesions as a consequence of repeated damage. Therefore, in our prediction model, the accuracy of RAP recurrence prediction is positively correlated with β2-MG, why which is it negatively related to CRP? This may be associated with pancreatic fibrosis after repeating recurrence of RAP. There is further emerging evidence to suggest that pancreatic fibrosis reduces severity in acute-on-chronic pancreatitis. As such, recurrent attacks of pancreatitis may lead to increasing burden of parenchymal fibrosis, which in turn may be protective against the inflammatory cascade. Another speculated explanation is that protective immunological mechanisms are up-regulated in recurrent pancreatitis that not activates in the initial bout.
However, as a retrospective study predicting the recurrence of RAP, there were several limitations to the present study. Firstly, the present study was a single-center study enrolling limited number of patients. Secondly, our data lack dynamic follow-up during hospitalization and after discharging. Thirdly, CRP level is closely associated with the time of inflammation, but the measurement of CRP in our trial is the result of patients within 12 hours after admission, but the interval between onset and measurement is uniform. It may affect the results, or it may be one reason why the specificity and sensitivity of our prediction model are low. Eventually, this study only used biochemical detection technique, which may cause bias in the results. Further investigation using a multi-center and prospective study and involving radiomics technique is necessary in order to improve the accuracy of the results.