The epidemiology of pyogenic liver abscess has changed dramatically in recent years ( 1 ). Previously, although incidence was considered rare, the condition was associated with high illness and death rates, usually due to underlying hepatobiliary diseases and polymicrobial infection ( 2 ), with Escherichia coli as the major pathogen ( 3 ). More recently, investigations in Taiwan suggest the role of cryptogenic or primary liver abscess, i.e., abscesses without underlying hepatobiliary diseases, in pyogenic liver abscess ( 4 , 5 ). These reports also indicate that diabetes is the major predisposing factor of liver abscess and that Klebsiella pneumoniae is the primary pathogen. However, these results were obtained from small-scale hospital-based surveys, which could not provide a panoramic view of the disease. To confirm these observation-based results, we conducted a large-scale, unbiased investigation. In addition to epidemiology, the pathogenesis of liver abscess caused by Klebsiella spp. has also been extensively studied, but the mechanism is still not clear. MagA, an outer-membrane protein contributing to capsular polysaccharide formation, coexists with serotype K1 and has been identified as the major virulence factor of K. pneumoniae ( 6 ). MagA-positive (or serotype K1) K. pneumoniae is accordingly recognized as the main pathogen of pyogenic liver abscess ( 7 , 8 ). Nevertheless, how diabetes increases the risk for Klebsiella spp. liver abscess is still not clear. Further research is needed on whether pyogenic liver abscess is affected by immunocompromised conditions, such as malignancy, renal failure, postorgan transplantation, or HIV infection. To clarify the epidemiology and pathogenesis of pyogenic liver abscess, we used information gathered by the Taiwan National Health Insurance (NHI) program, which was initiated in 1995 by the government to cover most Taiwanese citizens. In 2005, 91.25% of healthcare providers were enrolled in the program and 99% of Taiwanese were insured ( 9 ). Consequently, since 1995, the program has obtained comprehensive health data on the population in Taiwan. In this study, we used NHI data to study the incidence and death rates caused by pyogenic liver abscess in Taiwan and to investigate factors modifying the manifestations of this disease. Methods Patients We requested data on patients with pyogenic liver abscess from the Taiwan NHI program. Cases were selected by using the following criteria: patients were hospitalized and reported before 2004, and the discharge diagnoses included abscess of liver per the International Classification of Diseases, 9th revision, Clinical Modication (ICD-9-CM 572.0) but excluded amebic liver abscess (ICD-9-CM 006.3). Though we selected cases documented up to the end of 2004, the database could not provide information from patients who had not yet been discharged. Those admitted before December 31, 2004, but discharged during or after 2005 were therefore not included in our database. This exclusion results in the underestimation of case-patients admitted at the end of 2004. Data on 29,965 case-patients were collected. After excluding patients discharged before 1996 and those without clear records regarding age or sex, we enrolled 29,703 case-patients in our study. Patient data were anonymous. Names of these patients were not included, and patient and healthcare provider identification numbers were encrypted. This primary set of data included the date of admission and discharge, age, sex, diagnoses (up to 5), procedures (up to 5), outcome at discharge (recovered or died), and the fees charged to patients. Laboratory data, including microbiologic data and medication, were not included. Any underlying diseases were determined by the diagnoses listed in the medical records, which were coded by ICD-9-CM. Because K. pneumoniae is the major pathogen of primary pyogenic liver abscess in Taiwan, it is expected to play an important role in the pathogenesis and prognosis of this disease. Unfortunately, the NHI database does not include microbiologic data. To compensate for this, we reviewed the records of patients in National Taiwan University Hospital (NTUH). This hospital is a public medical center in Taipei, functioning both as a primary care hospital and as a tertiary referral center ( 10 ). As the leading hospital in Taiwan ( 10 ) with a 113-year history ( 11 ), NTUH serves patients and accepts referrals evenly distributed from every part of Taiwan. The hospital provides care for ≈2,000 inpatients and 7,000 outpatients a day ( 11 ), which are ≈3.5% and 2%, respectively, of persons included in the NHI database ( 12 ). Therefore, the patients of NTUH are representative of all of the patients in Taiwan, without substantial bias but may be skewed slightly to the severe side. We selected case-patients from this hospital using the same criteria mentioned above, except that the discharge year was between January 1, 2000, and December 31, 2004; complete microbiologic data was preserved in the NTUH laboratory only after 2000. These patients were included in the NHI database anonymously. For case-patients from NTUH, we reviewed actual medical records and obtained microbiologic data from the hospital’s laboratory. Statistical Analysis Numerical data were compared by Student t test or paired t test. Categorical data were processed by χ2 test. Pearson correlation coefficients and χ2 goodness-of-fit test were used to estimate the trend of incidence and death over time. Unfortunately, incidence and death from different years could not be directly compared because the population structure changed slightly over the study period. To correct the bias, we calculated age-standardized incidence and death rates. The correction was based on age-specific population data in 1996. Finally, risk factor analysis was conducted by using the binary logistic regression and curve estimation methods by SPSS version 11.0 for Macintosh (SPSS, Inc. Chicago, IL, USA). Results Demographic Data A total of 29,703 case-patients from the NHI database were enrolled in our analysis (Table 1). Ages of these patients ranged from 85 years of age. Incidence and Risk Factors The gross incidence of pyogenic liver abscess from 1996 through 2004 was 14.87 cases/100,000 population/year (17.94 male cases/100,000 population and 11.65 female cases/100,000 population). The annual increase of incidence was 0.86 cases/100,000 population (r = 0.98, p 5 underlying diseases. For this reason, some minor conditions, such as peptic ulcer, urinary tract infection, and hypertension, paradoxically decreased death rates in our data. Third, in contrast to the comprehensive data of pyogenic liver abscess, detailed health data for each person in the population are not available. We are therefore unable to estimate the interaction among the risk factors of pyogenic liver abscess in the population (Table 3). Nevertheless, this study still provides a clear picture of pyogenic liver abscess in Taiwan. The rapid and steady increase of cases with pyogenic liver abscess in Taiwan should be noted (Table 2). Although the prognosis of liver abscess patients has improved over time (Figure 3), pyogenic liver abscess-related death in the population continues to increase (Table 2). Furthermore, complex interactions between pyogenic liver abscess, diabetes, renal disease, and malignancy are shown to worsen this condition. Further collaboration among clinical medical practitioners, public health workers, and research scientists is mandatory to fight against such a challenge in the future.
