To the best of our knowledge, this is the first systematic review and meta-analysis of the incidence of liver abscess formation after TACE. We found that the incidence of liver abscess formation after TACE was 0.54%. Subgroup analyses showed that this incidence was higher among studies that were of high quality and was lower in studies with large sample sizes.
It's worth noting that we found a higher incidence of liver abscess formation after DEB-TACE compare to C-TACE, although the difference was not statistically significant. Previous studies have shown that 100–300 µm CalliSpheres DEBs were more likely to cause liver abscesses than those with a size of 300–500 µm[24, 43]. However, the existing data are insufficient for further grouping and analysis based on DEB size. Another interesting finding was that the incidence of the disease was higher in Europe and America than in Asia, but the difference was not statistically significant.
Results of previous studies have indicated that type 2 biliary abnormality is a risk factor for liver abscess formation after TACE[4, 11]. Our results support this possibility; the OR was reported to be as high as 133.69. Some studies have shown that Oddi sphincter dysfunction or incision enables intestinal bacteria to enter (in a retrograde manner) and colonize the bile duct[4, 44]. Moreover, the local toxicity of chemoembolic agents and the embolization of vessels feeding the bile duct as a result of TACE may lead to bile duct injury[45]. Bile duct injury after TACE may enable opportunistic pathogens to colonize the bile duct and enter the liver parenchyma, where they proliferate rapidly within the local ischemic and hypoxic microenvironment after TACE, thus leading to liver abscess formation.
This study revealed that the incidence of liver abscess formation after TACE was significantly increased among patients with liver metastases. Ye et al. reported that for patients with liver metastases, systemic chemotherapy within 3 months before TACE was an independent risk factor for liver abscess formation[10]; moreover, some patients with liver metastases had type 2 biliary abnormalities, both of which increase the risk of liver abscess in patients with liver metastases. The relatively higher probability of liver abscess formation should therefore be considered when TACE is performed in patients with liver metastases.
Furthermore, our data showed that PA treatment was protective against liver abscess formation; however, PA treatment is unreasonable and unnecessary for all patients with TACE. PA has been shown to reduce the incidence of liver abscess formation in patients with type 2 biliary abnormalities[7, 46]. Moreover, previous studies have shown that the incidence of liver abscess formation does not increase among patients without type 2 biliary abnormalities who do not receive PAs[47, 48]. Therefore, stratification according to risk factors is more reasonable for the administration of PAs before TACE.
The pooled mortality rate of liver abscess formation after TACE was 7.73%, and the main causes of death included septic shock and acute liver failure[5, 39, 42]. The mortality rate reached > 50% in the 1990s but dropped significantly to 9.65% between 2001 and 2010 and to 5.48% in the past decade. We hypothesize that the mortality rate has decreased because of improved understanding of the disease and advances in its treatment.
Our study has several strengths. First, to the best of our knowledge, this is the first study to report the incidence of liver abscess formation after TACE. Second, we pooled the risk factors for liver abscess formation after TACE based on the results of other studies, thereby focusing on relevant factors that could be recognized and addressed. Finally, for the first time, the mortality rate of liver abscess was shown to have decreased progressively over time.
However, our study has some limitations. First, we found considerable (I² = 89%) and significant (p < 0.01) heterogeneity among the studies with regard to the incidence of liver abscess formation after TACE. Second, the incidence findings must be interpreted with caution owing to the relatively small number of prospective studies, which might be a potential source of significant bias. Third, Finally, we could not study other factors that might have acted as predisposing factors for liver abscess (e.g., size and number of tumors, embolism materials, and diabetes) because of inadequate information.