INTRODUCTIONA pyogenic liver abscess (PLA) is a serious life-threatening condition, with a mortality rate of 6% to 14% [12]. With recent advances in diagnostic tools and treatment modalities, most cases are currently diagnosed at early stages and effectively treated. However, severe complications including endophthalmitis, metastatic central nervous system infections, psoas abscesses, splenic abscesses, abscess rupture, and septic pulmonary emboli may develop in some patients [3456].
Endogenous endophthalmitis (EE) is the most common and serious septic complication of PLA [78]; in a previous study, the reported incidence was 0.84% during 1 year of PLA follow-up [9]. EE is initially associated with subacute visual impairment, leading to loss of vision (blindness) despite aggressive treatment [8]. Factors suggested to be prognostic of visual outcomes in EE patients include initial visual acuity, early diagnosis, and vitrectomy [10]. Therefore, failure to make a timely diagnosis and to intervene at an early stage pose substantial risks to affected patients.
Little information on risk factors for EE in PLA patients is available. Diabetes mellitus (DM) and Klebsiella pneumoniae infection have been reported to be independent risk factors [8]. However, other studies have found that DM may not independently predict EE [911], and culture of K. pneumoniae may require a relatively long period of time. Therefore, we investigated risk factors for EE in PLA patients, to facilitate rapid diagnosis.
METHODSPatientsA total of 698 patients diagnosed with PLA were admitted to the Division of Gastroenterology of the Chonnam National University Hospital in Gwangju between January 2004 and July 2013; 72 patients were excluded because laboratory data were incomplete at the end of their follow-up periods, or PLA was difficult to distinguish from metastatic liver cancer, cholangiocarcinoma, or cystadenoma. Demographic information, laboratory data, imaging results, the treatment modalities chosen, microbiological results, and visual outcomes were retrospectively collected from medical records.
Diagnosis of PLA and EEPLA was diagnosed using sonography, computed tomography, or both modalities. Radiographic reports were retrospectively reviewed to determine the location and number of abscesses. The anatomy of the affected liver segment was described using the Couinaud classification [12]. Multiple abscesses were diagnosed when more than one abscess was evident in either the same or different lobes. Systemic infection was defined as PLA with a sequela of sepsis or septic embolization to the spleen, kidney, brain, and/or lung. A systemic infection was diagnosed using laboratory and radiological data, and via culture of fluid from an involved site.
If EE was suspected, an ophthalmologic consultation was scheduled on the request of either a physician or a patient. The thorough ophthalmologic examination included assessment of visual acuity, slit-lamp biomicroscopy, measurement of intraocular pressure, indirect ophthalmoscopy, and ultrasonography if needed.
Microbiological analysisBlood and abscess cavity fluid were subjected to culture of aerobic and anaerobic organisms using standard techniques. All identified organisms were assumed to play etiological roles.
Treatment of liver abscesses and endophthalmitisThe primary therapeutic modality was either percutaneous drainage or open surgery. If neither of these procedures was performed, management featured (appropriate) antibiotic therapy only. Intravenous and intravitreal antibiotics were given on suspicion of EE. Pars plans vitrectomy and/or evisceration were performed at the discretion of treating ophthalmologists.
Ethics statementThe Institutional Review Board of Chonnam National University Medical School approved the present study (approval no. CNUH-2014-030).
Statistical analysisThe liver abscess-associated endogenous endophthalmitis (LAEE) and non-LAEE groups were compared. Continuous variables (e.g., age) are expressed as means ± standard deviations. Appropriate statistical tests (Student t test, Pearson chi-square test, or the Mann-Whitney U test) were used to compare the baseline characteristics of patients in the two groups. Factors that were significant upon univariate logistic regression were entered into stepwise multivariate logistic regression to identify independently significant EE predictors. Statistical significance was accepted when the p < 0.05, or equivalently, when the 95% confidence interval (CI) of the odds ratio (OR) excluded unity. Statistical analyses were performed using SPSS version 20.0 (IBM Co., Armonk, NY, USA).
RESULTSPatient characteristicsThe characteristics of the 626 PLA patients (373 males, 59.6%; 253 females, 40.4%) are shown in Table 1. The mean patient age was 62.8 ± 13.6 years. Underlying conditions included DM in 153 patients (24.4%), a history of alcohol consumption in 206 (32.9%), biliary tract disease in 210 (33.5%), a previous hepatobiliary procedure/operation in 138 (22%), and another systemic infection in 92 (14.7%). These latter infections were sepsis (n = 51, 8%); and infections of the lung (n = 33, 5.2%), kidney (n = 12, 1.9%), brain (n = 2, 0.3%), abdominal cavity (n = 4, 0.6%), and spine (n = 1, 0.2%).
Of the 92 patients, eight had multiple metastatic infections (five at two metastatic sites and three at three such sites). Overall, 464 patients (74.1%) had right lobe liver abscesses, 252 had (40.3%) left lobe abscesses, and 157 (25.1%) had multiple liver abscesses. Of the 626 patients, 247 (39.5%) underwent percutaneous drainage, five (0.8%) underwent surgical drainage, and 374 (59.7%) received antibiotics only.
Of the 626 patients, 12 (1.92%) were diagnosed with LAEE. The proportions of patients with a systemic infection (p = 0.004), K. pneumoniae infection (p = 0.015), an abscess in the right superior segment (p = 0.037), and DM (p = 0.048) were all significantly higher in the LAEE group.
Initial symptoms, management, and visual outcomes of EE patientsThe most common initial symptoms were blurred vision and ocular pain (Table 2). Ocular symptoms developed prior to the diagnosis of liver abscesses in eight patients (66.7%). Initial visual problems were chemosis only in one patient, ocular pain in two, blurred vision in nine, and light perception only in one. The interval between EE diagnosis and intravitreal antibiotic injection/vitrectomy was less than 24 hours. Appropriate systemic and intravitreal antibiotics were prescribed for nine patients; the antibiotics included ceftazidime 2.25 mg/0.1 mL and vancomycin 1 mg/0.1 mL (Fig. 1). Pars plana vitrectomy was performed in three patients. Enucleation or evisceration was performed to relieve pain or infection in four. The final visual outcomes were no light perception in seven patients, hand motion only in three, and decreased visual acuity in two. Early intravitreal antibiotic injection or vitrectomy preserved useful vision. The details are shown in Table 2.
Risk factors for LAEEUnivariate logistic regression showed that the presence of another systemic infection (OR, 6.13; p = 0.002), K. pneumoniae infection (OR, 4.29; p = 0.018), an abscess in the right superior segment (OR, 4.9; p = 0.041), and underlying DM (OR, 3.17; p = 0.048) were significant risk factors for EE in PLA patients.
Multivariate logistic regression confirmed that the presence of another systemic infection (OR, 5.52; p = 0.005), an abscess in the right superior segment (OR, 5.26; p = 0.035), and K. pneumoniae infection (OR, 3.68; p = 0.039) were significant risk factors for LAEE in PLA patients (Table 3).
Microbiological analysisThe culture rate from abscess pockets of the non-LAEE group was 66.4% (146/220) and that of the LAEE group was 66.7% (6/9). The blood culture rate in the non-LAEE group was 30.4% (175/575) and that in the LAEE group was 27.3% (3/11).
K. pneumoniae, Streptococcus species, and Enterococcus species were the most common organisms in pus of both groups. Bacteremia was evident in 174 patients (27.8%). K. pneumoniae and Escherichia coli were the most commonly isolated organisms from both groups. The culture rate of K. pneumoniae from abscess pockets was 55.5% (121/218) and that from blood was 21.7% (125/575).
DISCUSSIONAn important novel finding of the present study is that the presence of another systemic infection, an abscess in the right superior segment, and K. pneumoniae infection were all significantly associated with LAEE, facilitating early prediction of EE development and allowing the visual outcomes of patients with PLA to be partly preserved.
The prevalence of EE in PLA patients of the present study was 1.92%, comparable to the values of previous studies (0.84% to 6.9%) [69]. One large population-based study that explored the epidemiological association between PLA and EE found that about 0.84% of PLA patients developed EE during a 1-year follow-up period [9]. EE is generally uncommon, but is the most frequent serious septic complication of PLA [7], and the outcome is usually dismal. Despite early diagnosis of EE in PLA patients, visual outcomes are generally poor. However, useful vision can be preserved in patients treated with intravitreal antibiotic injections or vitrectomy. The alternative is legal blindness.
Consistent with the results of previous studies [1314], K. pneumoniae was the bacterium most commonly isolated from pus and blood. Fifty percent of patients with LAEE were infected with K. pneumoniae; endogenous K. pneumoniae endophthalmitis is the most common metastatic infection from a K. pneumoniae liver abscess [15], which has emerged as the most common pathogen of liver abscesses in Taiwan [413]. KLAs are becoming more common in other countries of southeast Asia, including Korea, Singapore, Japan, and Thailand, and they constitute an emerging infectious disease in the United States and elsewhere worldwide [1617]. The frequency of K. pneumoniae culture was lower in the present study than in previous works [18], but it is possible that some patients underwent antibiotic therapy at other facilities prior to transfer to our tertiary referral center.
DM and K. pneumoniae infection have been reported to be independent risk factors for the development of EE in PLA patients [8]. Consistent with the data of other studies, we found that DM and the K. pneumoniae infection rate were significantly higher in the LAEE group. Although DM and K. pneumoniae infection (in particular, infection by serotype K1) have previously been suggested to be risk factors for EE development in PLA patients, the detailed mechanisms remain unclear. The virulence of the K1 strain is enhanced by production of a mucoviscous exopolysaccharide web that exhibits hyper-mucoviscosity, high-level resistance to phagocytosis by macrophages and neutrophils, and resistance to complement deposition [1920]. In addition, diabetes interferes with chemotaxis by polymorphonuclear leukocytes and impairs phagocytosis of K. pneumoniae strains of capsular serotype K1 or K2 in patients with poor glycemic control [21]. However, although we found that K. pneumoniae infection was a risk factor for LAEE, as did previous studies [7], DM was not significantly associated with LAEE in the present study.
This is the first study to show that the presence of another systemic infection and an abscess in the right superior segment are significantly associated with LAEE. Such clinical features may aid in the early diagnosis of LAEE; unfortunately, K. pneumoniae cultures grow rather slowly. Systemic infection is considered characteristic of liver abscesses caused by K. pneumonias of serotype K1, and such abscesses are a well-known risk factor for EE [3]. It is possible that the observed systemic infections are propagated via the inferior vena cava (IVC); the right superior segment is anatomically close to the IVC and the hepatic vein of the right superior segment and the IVC are obtusely angled. Our results thus suggest that the risk of EE development should be considered in PLA patients with other systemic infections and abscesses of the right superior segment. Physicians should be alert to the possible development of EE when a PLA patient with these risk factors complains of ocular symptoms.
Our study had certain limitations. First, we retrospectively analyzed data collected in a single center; therefore, our results may be inapplicable to other patient populations. Second, our sample sizes were small, especially that of the LAEE group, making it difficult to effectively compare outcomes between the two groups. Third, we did not perform K. pneumoniae genotypic analysis (for example, we did not search for the K1 strain). Fourth, the frequency of K. pneumoniae culture in the present study was lower than those of previous studies. Larger prospective studies are required to confirm the translational utility and applicability of our findings.
In conclusion, the prevalence of EE in patients with PLA was 1.92%. PLA patients with other systemic infections, abscesses in the right superior segment, and K. pneumoniae infections require close monitoring and early intervention to treat LAEE. Prompt intervention such as intravitreal antibiotic injection or early vitrectomy may salvage useful vision.