Aspirin use is associated with reduced risk for recurrence of pyogenic liver abscess: a propensity score analysis

Abstract

Aspirin possesses anti-bacterial activity that may prevent recurrence of Klebsiella pneumoniae pyogenic liver abscess (KP-PLA). In ex-vivo study, aspirin was administered before bactericidal assay against serotype K1 K. pneumoniae. We identified 5,912 patients with PLA who had no known pre-existing hepatobiliary diseases or malignancy in Taiwan from 1999 to 2013 from nationwide cohort study. Multivariate Cox proportional hazards regression models was used to estimate the hazard ratios [HR] for the association between aspirin use and recurrent PLA. The PLA recurrence rate in patients taking aspirin daily for 30 or more days, from 90 days before to 90 days after the first PLA episode (aspirin users), and aspirin non-users was 42.5 and 74.6 per 1,000 person-years of follow-up, respectively. The population-based study showed a HR for PLA recurrence in aspirin users of 0.50 (95% confidence interval, 0.35-0.69), relative to that in non-users, after adjustments for confounders. An ex-vivo study indicated that aspirin was able to significantly enhance bacterial killing by leukocytes, whether collected from diabetic patients with KP-PLA recurrence or from healthy volunteers. Our results suggest that aspirin is associated with reduced risk for PLA recurrence among Taiwanese with PLA who had no preexisting hepatobiliary diseases or malignancy.

Figure 1

Flow chart of study cohort. Note: LHID, Longitudinal Health Insurance Database.

Figure 2

(A) Cumulative proportion of patients developing recurrent pyogenic liver abscess events during follow-up according to aspirin uses and non-uses, before propensity-score matching. Kaplan-Meier analysis for cumulative incidence of pyogenic liver abscess recurrence showed significantly lower risk in the aspirin users group than in the non-users group before propensity-score matching (p < 0.001). (B) Cumulative proportion of patients developing recurrent pyogenic liver abscess events during follow-up according to aspirin users and non-users, after propensity-score matching. Kaplan-Meier analysis for cumulative incidence of pyogenic liver abscess recurrence showed significantly lower risk in the aspirin users group than in the non-users group after propensity-score matching (p = 0.014).

Figure 3

Dose-response association between oral anti-diabetic drug use (daily defined dose) and hazard ratio for recurrent pyogenic liver abscess in diabetic patients. Aspirin use was associated with lower risk for recurrent pyogenic liver abscess, especially in diabetic patients who did not receive an oral anti-diabetic drug (OAD) or those who received a high OAD dose for sugar control. Aspirin use did not show a significant difference in risk for recurrent pyogenic liver abscess in a comparison between diabetic patients with and without insulin therapy. Note: ddd, daily defined dose.

Figure 4

Ex-vivo human leukocyte bactericidal activity assay. Peripheral WBCs from 5 diabetic patients with recurrent pyogenic liver abscess caused by KP and 5 healthy volunteers (controls) were collected before and 1 h after oral administration of 100 mg of ASA, and were incubated with KP that had previously been opsonized with normal human serum. ASA treatment significantly enhanced leukocyte killing of KP (p < 0.01), regardless of whether leukocytes were collected from patients or healthy volunteers. Note: ASA, aspirin; KP, Klebsiella pneumoniae; WBC, white blood cells.