Risk factors for developing acute cholangitis
When there is no biliary obstruction, simple biliary infection can be asymptomatic. Once acute cholangitis develops, it rapidly progresses to systemic inflammatory response syndrome (SIRS), sepsis and even death if it is not recognized and treated properly in the early stage[6]. Thus, it is critical to promptly identify patients who may easily progress to acute cholangitis. The previous diagnosis of acute cholangitis was based on Charcot’s triad. Although it has a specificity higher than 90%[7], its sensitivity is only 25%[8–10]. In this study, the diagnostic criteria for acute cholangitis referred to the 2018 Tokyo Guidelines[11], which exhibit good sensitivity (95.1%) but poor specificity (66.3%). In this study, the factors that may lead to choledocholithiasis in patients with acute cholangitis were first analyzed by single-factor analysis. Compared with patients in the choledocholithiasis group, patients in the acute cholangitis group were significantly more likely to be male, ≥ 70 years old, have a smoking history, have hypertension, have fever (> 38°C) and/or shaking chills, have a duodenal peripapillary diverticulum, and have a maximum diameter of choledocholithiasis (≥ 10 mm) (P < 0.05). Furthermore, the acute cholangitis group had significantly greater WBC, CRP, T-Bil, ALT, AST, ALP, GGT, Scr, PT, and D-D levels (P < 0.05) and significantly lower Alb levels (P < 0.05). However, single-factor analysis cannot control the influence of other factors on the observation indicators, which may enhance or weaken the effect of the observation indicators. Logistic regression analysis of the above indicators with P < 0.05 was performed. Logistic regression analysis revealed that the maximum diameter of choledocholithiasis (≥ 10 mm), T-Bil, CRP, WBC, fever (> 38°C) and/or shaking chills, male sex, AST and ALP were independent risk factors for acute cholangitis (P < 0.05).
(1) Maximum diameter of choledocholithiasis (≥ 10 mm)
The most common risk factor for acute cholangitis is choledocholithiasis[3]. The underlying mechanism may be that common bile duct stones block the bile duct, interfere with the enterohepatic circulation of bile, increase the pressure in the bile duct[10], and cause bile vein and bile lymph reflux[12, 13], which subsequently leads to bacterial transcription in the bile duct. At present, there are few reports about the relationship between the diameter of choledocholithiasis and the risk of acute cholangitis. A previous study included a maximum diameter of choledocholithiasis (≥ 10 mm) as one of the risk factors for acute suppurative cholangitis[14]. In our study, we found that a maximum diameter of choledocholithiasis (≥ 10 mm) was an independent risk factor for acute cholangitis.
(2) T-Bil
When acute cholangitis occurs, the inflammatory reaction in the body tends to be severe. Some scholars[15–17] believe that inflammatory factors secreted by bile duct cells, such as TNF and IFN γ, can promote periodontal inflammation and inhibit the transport of chloride and bicarbonate ions in bile duct cells, thus hindering the flow of bile and resulting in hyperbilirubinemia. On the other hand, the central cause of acute cholangitis is biliary obstruction. Biliary obstruction and inflammation lead to an increase in bilirubin. The 2018 Tokyo Guidelines provided a grading system for severity, and T-Bil was included in this system[11]. T-Bil was also reported to be associated with in-hospital death[18]. Thus, we speculated that total bilirubin may be an independent risk factor for acute cholangitis. Our results confirmed this supposition. At the same time, the ROC curve was generated. The results indicated that acute cholangitis was most likely to occur when T-Bil was > 34.25 µmol/L.
(3) WBC, CRP, fever (> 38°C) and/or shaking chills
As indicators of inflammatory reactions, these indicators have high value in identifying choledocholithiasis with acute cholangitis. In particular, when the body temperature of patients with choledocholithiasis is more than 38°C and/or shaking chills occurs, acute cholangitis may occur. When CRP was > 10.85 mg/L, the sensitivity of diagnosing acute cholangitis was 93.7%, with a specificity of 74.9%. The area under the curve was 0.869. When the WBC count was > 9.95×109/L, the sensitivity of diagnosing acute cholangitis was 78.6%, with a specificity of 90.8%. The area under the curve was 0.835. Therefore, it is essential to administer timely medical and bile duct drainage treatment.
(4) Male sex
The relationship between sex and acute cholangitis is not very clear. A large-scale study in the United States suggested that more than half of the hospitalized patients with acute cholangitis were over 60 years old, of which men accounted for the majority[2]. Another study also reported that men were more prone to developing acute cholangitis than women among patients with choledocholithiasis [19]. The results of this study also suggested that male sex was a risk factor for acute cholangitis, which may be related to androgen levels, anatomy of the biliary system, lifestyle and so on.
(5) AST and ALP
hepatocytes in the human body are linked by tight junctions, which are essential for maintaining the function of hepatic cells. By contributing as gatekeepers for paracellular diffusion between adherent hepatocytes and cholangiocytes, the blood-biliary barrier is shaped[20]. In patients with acute cholangitis, the pressure in the bile duct tends to be high. When the pressure in the bile duct rises to a certain level, the intercellular structure of the hepatocytes and the blood bile duct barrier may be destroyed, followed by patchy necrosis of hepatocytes, cholestasis and changes in liver function[21]. In this study, AST and ALP were found to be independent risk factors for developing acute cholangitis. When AST was > 57.8 U/L, the sensitivity of diagnosing acute cholangitis was 86.2%, with a specificity of 60.9%. The area under the curve was 0.765. When the ALP concentration was > 162.5 U/L, the sensitivity of diagnosing acute cholangitis was 82.4%, with a specificity of 60.2%. The area under the curve was 0.743.
There are still some limitations in this study, such as the insufficient number of cases collected and the insufficient comprehensiveness of the collected data. It is not clear whether there are other possible risk factors for acute cholangitis.