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Pneumonia is an independent risk factor for pyogenic liver abscess: A population-based, nested, case-control study

  • Sai-Wai Ho,

    Affiliations Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

  • Chao-Bin Yeh,

    Affiliations Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

  • Shun-Fa Yang,

    Affiliations Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

  • Han-Wei Yeh,

    Affiliation School of Medicine, Chang Gung University, Taoyuan City, Taiwan

  • Jing-Yang Huang,

    Affiliation Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

  • Ying-Hock Teng

    Affiliations Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

Pneumonia is an independent risk factor for pyogenic liver abscess: A population-based, nested, case-control study

  • Sai-Wai Ho, 
  • Chao-Bin Yeh, 
  • Shun-Fa Yang, 
  • Han-Wei Yeh, 
  • Jing-Yang Huang, 
  • Ying-Hock Teng



Bacteremic pneumonia is considered a potential cause of distal organ abscess formation. Therefore, we hypothesize that pneumonia is a risk factor for pyogenic liver abscess (PLA).The aim of this study is to explore the association between pneumonia and PLA.

Methodology/Principal findings

A nationwide, population-based, nested, case–control study was conducted using data from the Taiwan National Health Insurance Research Database. In total, 494 patients with PLA and 1,976 propensity score matched controls were enrolled. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) in patients with exposure to pneumonia before PLA. After matched and adjusted for confounding factors including age, sex, urbanization, income, chronic liver disease, alcohol-related disease, biliary stone, chronic kidney disease, diabetes mellitus, chronic liver disease, and cancer, hospitalization for pneumonia remained an independent risk factor for PLA with an aORs of 2.104 [95% confidence interval (CI) = 1.309–3.379, p = 0.0021]. Moreover, the aORs were significantly higher among patients hospitalized for pneumonia within 30 days (aORs = 10.73, 95% CI = 3.381–34.054), 30–90 days (aORs = 4.698, 95% CI = 1.541–14.327) and 90–180 (aORs = 4.000, 95% CI = 1.158–13.817) days before PLA diagnosis.


Pneumonia is an independent risk factor for subsequent PLA. Moreover, hospitalization for pneumonia within 180 days before PLA diagnosis was associated with an increased risk of PLA.


Pyogenic liver abscess (PLA) is a potentially fatal bacterial infection of the hepatic parenchyma, with a 5.6%–23% mortality rate [1, 2]. Moreover, complications, such as metastatic infection to the lungs, central nervous system, and eyes, increase patient morbidity and mortality [3, 4]. Most PLA cases develop because of systemic bacteremia or intraabdominal infections [5]. An immunocompromised status, diabetes mellitus, liver cirrhosis, and advanced age are well-known predisposing risk factors for PLA [6, 7].

However, the etiologies of and risk factors for PLA have continued to evolve; recently reported risk factors include zolpidem and proton pump inhibitor use and splenectomy [810]. In Taiwan, the most common pathogen of PLA has also changed from Escherichia coli to Klebsiella pneumoniae since the 1980s [11]. Notably, in addition to causing PLA, K. pneumoniae is also a dominant pathogen of bacteremic community-acquired pneumonia in Taiwan [12]. In South Africa, pneumonia accounted for up to 62% of K. pneumoniae bacteremia [13]. Furthermore, many pneumonia survivors may acquire bacterial infections after their original pneumonia infection. Brain abscess, psoas muscle abscess, para-aortic arch abscess, thyroid abscess, splenic abscess, and infraorbital abscess have been reported after pneumonia [1419]. Bacteremic pneumonia is considered a potential cause of distal organ abscess formation. Therefore, we hypothesize that pneumonia is a risk factor for PLA.

Understanding the risk factors for PLA is clinically crucial because rapid diagnosis followed by appropriate management of PLA can improve patient outcomes and prevent complications. Here, we conducted a case–control study by using a national database from Taiwan and explored the association between pneumonia and PLA.

Materials and methods

Database and settings

This nested case–control study was conducted using registration and claims data of 2009–2013 obtained from the Longitudinal Health Insurance Database 2010 (LHID2010), a subset of the National Health Insurance (NHI) Research Database (NHIRD), managed by the Taiwanese National Health Research Institutes. This dataset contains all information regarding sociodemographic status such as sex and date of birth; outpatient, inpatient, and emergency care; and prescription drugs of 1 million of the NHIRD beneficiaries, randomly sampled from the 2010 registry of 23 million of the NHIRD beneficiaries. The disease diagnosis is based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The diagnosis coding in this dataset is highly reliable because all insurance claims have been monitored by medical reimbursement specialists and through peer review. Our study protocol was approved by the Institutional Review Board of Chung Shan Medical University Hospital (CSMU No.: 15061). The requirement for written informed consent from the participants was waived because the LHID2010 contains deidentified data.

Study population

Adult patients aged >20 years diagnosed as having new onset PLA (ICD-9-CM: 572.0) between January 2010 and December 2013 were categorized as the case group. The date of first hospitalization for PLA was defined as the index date. Patients with previous PLA diagnoses in the data set before January 2010 were excluded (n = 141).

For each PLA case, the first round matching was conducted to select controls at a 1:100 full matching by age, sex, urbanization and income. The second round matching was applied to reduce the confounding of co-morbidities such as diabetes mellitus (DM; ICD-9-CM: 250), chronic liver disease (ICD-9-CM: 456.0–456.2, 571.2, and 571.4–571.6), chronic kidney disease (CKD; ICD-9-CM: 582, 583, 585, 586, and 588), biliary stone (ICD-9-CM: 574), chronic obstructive pulmonary disease (COPD; ICD-9-CM: 490, 491, 492, and 494–496), alcohol-related disease (ICD-9-CM: 291, 303, 305.0, 357.5, 425.5, 535.3, 571.0–571.3, 655.4, and 760.71), and cancer (ICD-9-CM: 140–208) by 1:4 propensity score matching in each first round matching sub-groups. Patients with viral pneumonia (ICD-9-CM: 480, 487, 488 and 488.1) were excluded. Fig 1 illustrates our study framework.

Definition of pneumonia

We defined pneumonia (ICD-9-CM: 481, 482, 483, and 485–486) as the primary diagnosis, which required hospital admission and intravenous antibiotic treatment. A study demonstrated that the identification of inpatient pneumonia using this method has a positive predictive value of 88% [20].

Statistical analysis

Categorical variables were delineated as numbers and percentages and compared using the chi-squared or Fisher exact test, where appropriate. Continuous data were delineated as means ± standard deviations and compared using the independent t test. Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs) with a 95% confidence interval (CI) for case group compared with control group. In multivariate analysis, we adjusted for comorbidities that may have predisposed a patient to PLA. In the subsequent analyses, we stratified pneumonia events into the number of patients hospitalized for pneumonia and duration of the hospitalization. Statistical analysis was performed using SPSS (version 18.0; SPSS Inc., Chicago, IL, USA) and SAS (version 9.4; SAS Institute, Cary, NC, USA). A p value <0.05 indicated statistical significance.


After propensity score matching, a total of 494 cases of new onset PLA and 1,976 control patients without PLA were enrolled in this study for final analysis. Table 1 lists the demographic characteristics of the patients and their distribution in the case and control groups. The mean age was 60.11 ± 14.43 and 60.09 ± 14.46 years in the case and control group, respectively; no significant difference was noted in age, sex, and socioeconomic status between the two groups after matching. However, compared with the control group, the case group had a significantly higher proportion of the biliary stone (4.05% vs 2.02%) and previous hospitalization for pneumonia (5.67% vs 2.83%). During the study period, the trend of incidence of PLA was correlated to the trend of incidence of hospitalization for pneumonia (Fig 2).

Fig 2. Annual incidence of pyogenic liver abscess (PLA) in 2009–2013.

Table 2 showed the result by unconditional logistic regression analysis, hospitalization for pneumonia was an independent risk factor for PLA (aORs = 2.136, 95% CI = 1.289–3.537, p = 0.0032) after the adjustment for confounding factors, such as age, sex, urbanization, income, co-morbidities(including, COPD, alcohol-related disease, biliary stone, CKD, DM, chronic liver disease, and cancer). Another risk factors for PLA was biliary stone (aORs = 1.959, 95% CI = 1.112–3.452).

Table 2. Unconditional logistic regression of estimated odds ratios for PLA after propensity score matching.

Our main findings, the results of conditional logistic regression that adjusted for co-morbidities, are shown in Table 3. The aORs of PLA for exposure to pneumonia within 2 year prior to index date was 2.104 (95% CI = 1.309–3.379) in model 1. To further explore the association between hospitalization for pneumonia and PLA onset, the time interval between date of last hospitalization for pneumonia and the index date was calculated for each patient. The aORs for the time interval between hospitalization for pneumonia and PLA onset were listed, including hospitalized for pneumonia 30 days (aORs = 10.73, 95% CI = 3.381–34.054), 30–90 days (aORs = 4.698, 95% CI = 1.541–14.327) and 90–180 (aORs = 4.000, 95% CI = 1.158–13.817) days before the index date, were significantly higher than those of patients not hospitalized for pneumonia in model 2.

Table 3. Risk of pyogenic liver abscess in pneumonia patients by time interval between hospitalization for pneumonia and PLA onset.

Table 4 indicates the five specific models we used for subgroup analysis to explore the risk of PLA and number of pneumonia admissions within 1, 3, 6, 12, and 24 months before the index date. These five models demonstrated that patients having an increased number of hospitalizations for pneumonia before the index date had a significantly higher aORs for the development of PLA.

Table 4. Risk of pyogenic liver abscess in pneumonia patients by number of hospitalizations for pneumonia at specific time-point before index date.

Table 5 shows the underlying comorbidities of patients who were hospitalized for pneumonia in PLA and no PLA group. Compare with no PLA group, the ORs of pneumonia among all comorbidities were not higher in PLA group.

Table 5. Odds ratio of pneumonia and patient comorbidities in PLA and non-PLA group.

Table 6 lists the etiology and pathogens of pneumonia in patients hospitalized for pneumonia. Only the infection of K. pneumoniae demonstrated a significant difference between the case and control groups (p = 0.0383).

Table 6. Etiology and pathogens of pneumonia in patients hospitalized for pneumonia.


According to our review of relevant literature, this is the first study to demonstrate that previous hospitalization for pneumonia is an independent risk factor for subsequent PLA (aORs = 2.104, p = 0.0021) by using a nationwide administrative database. Our findings also demonstrate that time interval between hospitalization for pneumonia and PLA onset as well as the number of hospitalizations for pneumonia is associated with the risk of PLA.

A potential explanation for our results is the bacterial seeding that occurs in the hepatic parenchyma from the bloodstream during pneumonia. In Taiwan, Mycoplasma pneumoniae, Chlamydia pneumoniae, Streptococcus pneumoniae, and K. pneumoniae are common pathogens of community-acquired pneumonia [21]. Among these micro bacteria, K. pneumoniae is the pathogen most commonly isolated from patient with pneumonia of higher severity [12, 21]; it is also the major cause of bacteremic pneumonia and PLA in Taiwan. The situation in Taiwan is different from Western countries: the prevalence of liver abscess is lower in most Western populations [22]. In the United States, the most common bacterial pathogens of pneumonia are Strep. pneumoniae, M. pneumoniae, Staphylococcus aureus, and Legionella pneumophila [23]. Notably, K. pneumoniae infection is relative uncommon in Western populations [13]. The high rate of infection of the K1 and K2 capsular serotype strains of K. pneumoniae in East Asian countries may explain the aforementioned association between pneumonia and PLA in Taiwan [2426]. Our study also demonstrated a significant difference in K. pneumoniae pneumonia between the case and control groups, but these groups contained only 5 and 2 patients with K. pneumoniae infection, respectively (Table 6). This low prevalence of K. pneumoniae infection may have been underestimated because of the nature of the LHID2010. This dataset provides only the first four major ICD-9-CM codes of each patient for analysis. Here, we used ICD-9-CM codes of 482.0 and 041.3 to represent K. pneumoniae infection. Because this diagnostic code does not represent a specific disease, not all physicians key in this code but only the major disease code, potentially leading to selection bias. Furthermore, ICD-9-CM codes for infections of other bacteria, such as M. pneumoniae (ICD-9-CM: 483.0 and 041.81), C. pneumoniae (ICD-9-CM: 483.1) and Strep. pneumoniae (ICD-9-CM: 041.00–041.09 and 482.3) have been recorded inadequately in this data set. Thus, additional clinical studies are required for verifying the association between the etiology of pneumonia pathogens and liver abscess.

Another explanation for the development of PLA was the dysfunction of gut barriers during pneumonia. A previous study demonstrated that enterocyte injury is common in patients critically ill with pneumonia [27]. Therefore, after gut barrier dysfunction, bacteria may translocate to the liver through the portal vein system, eventually causing abscess formation in liver. DM patients are more likely to develop PLA because of their higher gut permeability [28]. Moreover, antibiotic therapy during pneumonia, which alters the composition and functions of gut microbiota and the intestinal immune system, eventually increases the risk of bacterial invasion [29]. Another potential mechanism contributing to PLA is the direct influence of pneumonia on the immune system. An immunocompromised status is a well-known potential risk factor for PLA. Studies have demonstrated that apoptosis of neutrophils and necroptosis of macrophages are common during bacterial pneumonia [30, 31].

A critical finding reported in this study is that hospitalization for pneumonia within 180 days before the index date was associated with an increased PLA risk. Our results also indicated that increased hospitalization for pneumonia was correlated with higher PLA risk. These findings are of clinical significance to physicians because a timely diagnosis of PLA is difficult [32]. The most common signs and symptoms of PLA, such as fever and abdominal pain, are nonspecific; even laboratory findings are nonspecific and non-diagnostic. PLA is usually diagnosed using imaging techniques such as sonography and computed tomography. This study established an association of pneumonia and development of PLA. A follow up imaging in selected patients treated for pneumonia may lead to early diagnosis of PLA especially if they have history of gall stones and symptoms suggestive of PLA.

The strength of this case–control study is that we used data from LHID2010, the subset of Taiwan National Health Insurance Research Database, a nationwide dataset comprising 1 million beneficiaries randomly selected from the 2010 NHI registry. The Taiwan NHI system, established in 1995, covers the medical expenses of approximately 98% of the population of Taiwan; therefore, the included data accurately represents conditions in Taiwan. Moreover, the LHID2010 has a longitudinal design to minimize selection biases. Furthermore, the possibility of recall bias was reduced by using the administrative database for analysis. In fact, several high quality articles publications were generated by this database set [3335].

Our study also has several limitations. First, the LHID2010 does not contain information regarding patients’ clinical presentation, laboratory data, microbiological culture data, and pneumonia severity index score; however, the risk of bacteremia is correlated with the severity of pneumonia. Second, although the cases and controls were matched with comorbidities, our sample size was insufficient to match for all comorbidities (Table 1); therefore, we performed multivariate analysis (Table 2, Table 3) to adjust for these potential confounding factors. Third, liver abscess is a disease endemic to Taiwan and East Asian countries; thus, our results may not be generalizable to Western populations. Fourth, small size of patient population and weakness of propensity matching methodology nature which does not account for unmeasured confounders in this study should be taken into consideration.

In conclusion, pneumonia is an independent risk factor for subsequent PLA. Moreover, hospitalization for pneumonia within 180 days before PLA diagnosis was associated with an increased PLA risk. Therefore, clinical physicians should consider PLA as a differential diagnosis for patients with infections after hospitalization for pneumonia.

Author Contributions

  1. Conceptualization: SWH CBY.
  2. Data curation: SFY HWY.
  3. Formal analysis: CBY.
  4. Funding acquisition: CBY.
  5. Investigation: YHT.
  6. Methodology: JYH.
  7. Software: JYH.
  8. Supervision: CBY.
  9. Writing – original draft: SWH, CBY.
  10. Writing – review & editing: SWH, CBY.


  1. 1. Meddings L, Myers RP, Hubbard J, Shaheen AA, Laupland KB, Dixon E, et al. A population-based study of pyogenic liver abscesses in the United States: incidence, mortality, and temporal trends. The American journal of gastroenterology. 2010;105(1):117–24. Epub 2009/11/06. pmid:19888200
  2. 2. Jepsen P, Vilstrup H, Schonheyder HC, Sorensen HT. A nationwide study of the incidence and 30-day mortality rate of pyogenic liver abscess in Denmark, 1977–2002. Alimentary pharmacology & therapeutics. 2005;21(10):1185–8. Epub 2005/05/11.
  3. 3. Lee SS, Chen YS, Tsai HC, Wann SR, Lin HH, Huang CK, et al. Predictors of septic metastatic infection and mortality among patients with Klebsiella pneumoniae liver abscess. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2008;47(5):642–50. Epub 2008/07/23.
  4. 4. Lin YT, Liu CJ, Chen TJ, Fung CP. Long-term mortality of patients with septic ocular or central nervous system complications from pyogenic liver abscess: a population-based study. PloS one. 2012;7(3):e33978. Epub 2012/04/06. PubMed Central PMCID: PMCPMC3313956. pmid:22479491
  5. 5. Lardiere-Deguelte S, Ragot E, Amroun K, Piardi T, Dokmak S, Bruno O, et al. Hepatic abscess: Diagnosis and management. Journal of visceral surgery. 2015;152(4):231–43. Epub 2015/03/17. pmid:25770745
  6. 6. Tian LT, Yao K, Zhang XY, Zhang ZD, Liang YJ, Yin DL, et al. Liver abscesses in adult patients with and without diabetes mellitus: an analysis of the clinical characteristics, features of the causative pathogens, outcomes and predictors of fatality: a report based on a large population, retrospective study in China. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2012;18(9):E314–30. Epub 2012/06/09.
  7. 7. Molle I, Thulstrup AM, Vilstrup H, Sorensen HT. Increased risk and case fatality rate of pyogenic liver abscess in patients with liver cirrhosis: a nationwide study in Denmark. Gut. 2001;48(2):260–3. Epub 2001/01/13. PubMed Central PMCID: PMCPMC1728191. pmid:11156650
  8. 8. Liao KF, Lin CL, Lai SW, Chen WC. Zolpidem Use Associated With Increased Risk of Pyogenic Liver Abscess: A Case-Control Study in Taiwan. Medicine. 2015;94(32):e1302. Epub 2015/08/13. PubMed Central PMCID: PMCPMC4616684. pmid:26266369
  9. 9. Wang YP, Liu CJ, Chen TJ, Lin YT, Fung CP. Proton pump inhibitor use significantly increases the risk of cryptogenic liver abscess: a population-based study. Alimentary pharmacology & therapeutics. 2015;41(11):1175–81. Epub 2015/04/15.
  10. 10. Lai SW, Lai HC, Lin CL, Liao KF. Splenectomy Correlates With Increased Risk of Pyogenic Liver Abscess: A Nationwide Cohort Study in Taiwan. Journal of epidemiology. 2015;25(9):561–6. Epub 2015/08/11. PubMed Central PMCID: PMCPMC4549607. pmid:26256773
  11. 11. Chang FY, Chou MY. Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-K. pneumoniae pathogens. Journal of the Formosan Medical Association = Taiwan yi zhi. 1995;94(5):232–7. Epub 1995/05/01. pmid:7613255
  12. 12. Lin YT, Jeng YY, Chen TL, Fung CP. Bacteremic community-acquired pneumonia due to Klebsiella pneumoniae: clinical and microbiological characteristics in Taiwan, 2001–2008. BMC infectious diseases. 2010;10:307. Epub 2010/10/27. PubMed Central PMCID: PMCPMC2987304. pmid:20973971
  13. 13. Ko WC, Paterson DL, Sagnimeni AJ, Hansen DS, Von Gottberg A, Mohapatra S, et al. Community-acquired Klebsiella pneumoniae bacteremia: global differences in clinical patterns. Emerging infectious diseases. 2002;8(2):160–6. Epub 2002/03/19. PubMed Central PMCID: PMCPMC2732457. pmid:11897067
  14. 14. Liu K, Yang C, Zhang Y, Yuan X, Xiao H, Bai Y, et al. Brain Abscess Following Intracerebral Hemorrhage in a Patient With Pneumonia. The Journal of craniofacial surgery. 2016. Epub 2016/10/19.
  15. 15. Shah SV. Community acquired Klebsiella pneumonia related PSOAS abscess. The Journal of the Association of Physicians of India. 2016;64(1):114–5. Epub 2016/10/12.
  16. 16. Koo KK, Sun JC, Whitlock RP, Franchetto AA, Mulji A, Lamy A. Para-aortic arch abscess secondary to Staphylococcus aureus pneumonia. The Canadian journal of cardiology. 2009;25(4):233–6. Epub 2009/04/03. PubMed Central PMCID: PMCPMC2706763. pmid:19340349
  17. 17. Cannizzaro MA, Veroux M, La Ferrera MG, Marziani A, Cavallaro N, Corona D, et al. Klebsiella pneumoniae pulmonary infection with thyroid abscess: report of a case. Surgery today. 2008;38(11):1036–9. Epub 2008/10/30. pmid:18958563
  18. 18. Izumikawa K, Morinaga Y, Izumikawa K, Hara K, Kohno S. A case of splenic abscess during treatment of interstitial pneumonia. Japanese journal of infectious diseases. 2006;59(5):320–2. Epub 2006/10/25. pmid:17060699
  19. 19. Chakravarty A, Salgia R, Mason E, Rajendran R, Muthuswamy P. Pneumonia and infraorbital abscess in a 29-year-old diabetic pregnant woman. Chest. 1995;107(6):1752–4. Epub 1995/06/01. pmid:7781379
  20. 20. Drahos J, Vanwormer JJ, Greenlee RT, Landgren O, Koshiol J. Accuracy of ICD-9-CM codes in identifying infections of pneumonia and herpes simplex virus in administrative data. Annals of epidemiology. 2013;23(5):291–3. Epub 2013/03/26. PubMed Central PMCID: PMCPMC3654522. pmid:23522903
  21. 21. Lee YT, Chen SC, Chan KC, Wu TC, Tsao SM, Chan CH. Impact of infectious etiology on the outcome of Taiwanese patients hospitalized with community acquired pneumonia. Journal of infection in developing countries. 2013;7(2):116–24. Epub 2013/02/19. pmid:23416657
  22. 22. Ali AH, Smalligan RD, Ahmed M, Khasawneh FA. Pyogenic liver abscess and the emergence of Klebsiella as an etiology: a retrospective study. International journal of general medicine. 2013;7:37–42. Epub 2014/01/01. PubMed Central PMCID: PMCPMC3873814. pmid:24379693
  23. 23. Marcos PJ, Restrepo MI, Anzueto A. Community-Acquired Pneumonia Requiring Hospitalization. The New England journal of medicine. 2015;373(24):2380–1. Epub 2015/12/10.
  24. 24. Yu VL, Hansen DS, Ko WC, Sagnimeni A, Klugman KP, von Gottberg A, et al. Virulence characteristics of Klebsiella and clinical manifestations of K. pneumoniae bloodstream infections. Emerging infectious diseases. 2007;13(7):986–93. Epub 2008/01/25. PubMed Central PMCID: PMCPMC2878244. pmid:18214169
  25. 25. Yeh KM, Kurup A, Siu LK, Koh YL, Fung CP, Lin JC, et al. Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan. Journal of clinical microbiology. 2007;45(2):466–71. Epub 2006/12/08. PubMed Central PMCID: PMCPMC1829066. pmid:17151209
  26. 26. Lin YT, Siu LK, Lin JC, Chen TL, Tseng CP, Yeh KM, et al. Seroepidemiology of Klebsiella pneumoniae colonizing the intestinal tract of healthy Chinese and overseas Chinese adults in Asian countries. BMC microbiology. 2012;12:13. Epub 2012/01/21. PubMed Central PMCID: PMCPMC3273430. pmid:22260182
  27. 27. Piton G, Belon F, Cypriani B, Regnard J, Puyraveau M, Manzon C, et al. Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality. Critical care medicine. 2013;41(9):2169–76. Epub 2013/06/21. pmid:23782971
  28. 28. Mooradian AD, Morley JE, Levine AS, Prigge WF, Gebhard RL. Abnormal intestinal permeability to sugars in diabetes mellitus. Diabetologia. 1986;29(4):221–4. Epub 1986/04/01. pmid:3519337
  29. 29. Theriot CM, Koenigsknecht MJ, Carlson PE Jr., Hatton GE, Nelson AM, Li B, et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nature communications. 2014;5:3114. Epub 2014/01/22. PubMed Central PMCID: PMCPMC3950275. pmid:24445449
  30. 30. Bordon J, Aliberti S, Fernandez-Botran R, Uriarte SM, Rane MJ, Duvvuri P, et al. Understanding the roles of cytokines and neutrophil activity and neutrophil apoptosis in the protective versus deleterious inflammatory response in pneumonia. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases. 2013;17(2):e76–83. Epub 2012/10/17.
  31. 31. Gonzalez-Juarbe N, Gilley RP, Hinojosa CA, Bradley KM, Kamei A, Gao G, et al. Pore-Forming Toxins Induce Macrophage Necroptosis during Acute Bacterial Pneumonia. PLoS pathogens. 2015;11(12):e1005337. Epub 2015/12/15. PubMed Central PMCID: PMCPMC4676650. pmid:26659062
  32. 32. Pang TC, Fung T, Samra J, Hugh TJ, Smith RC. Pyogenic liver abscess: an audit of 10 years' experience. World journal of gastroenterology. 2011;17(12):1622–30. Epub 2011/04/08. PubMed Central PMCID: PMCPMC3070135. pmid:21472130
  33. 33. Lee Y-T, Nfor ON, Tantoh DM, Huang J-Y, Ku W-Y, Hsu S-Y, et al. Herpes Zoster as a Predictor of HIV Infection in Taiwan: A Population-Based Study. PloS one. 2015;10(11):e0142254. pmid:26535574
  34. 34. Ou S, Shih C, Chao P, et al. EFfects on clinical outcomes of adding dipeptidyl peptidase-4 inhibitors versus sulfonylureas to metformin therapy in patients with type 2 diabetes mellitus. Annals of Internal Medicine. 2015;163(9):663–72. pmid:26457538
  35. 35. Lin J-N, Lin C-L, Lin M-C, Lai C-H, Lin H-H, Yang C-H, et al. Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study. The Lancet Oncology. 2015;16(13):1335–43. pmid:26321214