Trends in Hospitalizations for Clostridioides difficile Infection in End-Stage Liver Disease, 2005–2014

Abstract

Background

Data on the current estimates of the disease burden of Clostridioides difficile (C. difficile) infection in the setting of end-stage liver disease (ESLD) are emerging.

Aims

We examined the recent trends and predictors of hospitalizations and in-hospital mortality from C. difficile infection among hospitalizations with ESLD in the USA.

Methods

We performed a retrospective analysis using the National Inpatient Sample, 2005–2014. We defined ESLD and C. difficile infection using the International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariable logistic regression was used to determine the risk factors that impacted hospitalization and mortality.

Results

The prevalence of coding for C. difficile infection in decompensated cirrhosis increased from 1.3% in 2005 to 2.7% in 2014, with an annual rate of 7.8%. In hospitalizations with hepatocellular carcinoma, C. difficile infection increased steadily from 1.0 to 1.7% with an annual incremental rate of 6.4%. Among hospitalizations with ESLD, each passing 2-year period, increasing age, female, higher Charlson index, accompanying infection, hepatorenal syndrome, and ascites were associated with C. difficile infection. Although C. difficile infection was an independent predictor of in-hospital mortality during hospitalization with decompensated cirrhosis (odds ratio 1.53, 95% confidence interval 1.44–1.63), the proportion of in-hospital mortality during hospitalization with C. difficile infection and decompensated cirrhosis decreased from 15.4% in 2005 to 11.1% in 2014, with an annual rate of − 3.1% (95% CI − 5.7% to − 0.3%).

Conclusions

While the prevalence of C. difficile infection in hospitalized patients with ESLD increased approximately twofold, the in-hospital mortality decreased significantly during the past decade.

This is a preview of subscription content, access via your institution.

Fig. 1

Abbreviations

ESLD:

End-stage liver disease

HCC:

Hepatocellular carcinoma

NIS:

National Inpatient Sample

ICD-9-CM:

International Classification of Diseases, 9th Revision Clinical Modification

NAFLD:

Nonalcoholic fatty liver disease

APC:

Annual percentage change

CI:

Confidence interval

OR:

Odds ratio

References

  1. 1.

    Bosetti C, Levi F, Lucchini F, Zatonski WA, Negri E, La Vecchia C. Worldwide mortality from cirrhosis: an update to 2002. J Hepatol. 2007;46:827–839.

    Article  Google Scholar 

  2. 2.

    Mortality GBD. Causes of Death C. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117–171.

    Article  Google Scholar 

  3. 3.

    Kim D, Cholankeril G, Li AA, et al. Trends in hospitalizations for chronic liver disease-related liver failure in the United States, 2005–2014. Liver Int. 2019;39:1661–1671.

    Article  Google Scholar 

  4. 4.

    Kim D, Li AA, Perumpail BJ, et al. Changing trends in etiology-based and ethnicity-based annual mortality rates of cirrhosis and hepatocellular carcinoma in the United States. Hepatology. 2019;69:1064–1074.

    Article  Google Scholar 

  5. 5.

    El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(1264–1273):e1261.

    Google Scholar 

  6. 6.

    Kim D, Li AA, Gadiparthi C, et al. Changing trends in etiology-based annual mortality from chronic liver disease, from 2007 through 2016. Gastroenterology.. 2018;155:1154–1163.

    Article  Google Scholar 

  7. 7.

    Surawicz CM, Brandt LJ, Binion DG, et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013;108:478–498. (quiz 499).

    CAS  Article  Google Scholar 

  8. 8.

    Ziakas PD, Zacharioudakis IM, Zervou FN, Grigoras C, Pliakos EE, Mylonakis E. Asymptomatic carriers of toxigenic C. difficile in long-term care facilities: a meta-analysis of prevalence and risk factors. PLoS ONE. 2015;10:e0117195.

    Article  Google Scholar 

  9. 9.

    Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372:825–834.

    CAS  Article  Google Scholar 

  10. 10.

    Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198–1208.

    CAS  Article  Google Scholar 

  11. 11.

    Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55(Suppl 2):S88–92.

    Article  Google Scholar 

  12. 12.

    Bajaj JS, Ananthakrishnan AN, Hafeezullah M, et al. Clostridium difficile is associated with poor outcomes in patients with cirrhosis: A national and tertiary center perspective. Am J Gastroenterol. 2010;105:106–113.

    Article  Google Scholar 

  13. 13.

    Singal AK, Salameh H, Kamath PS. Prevalence and in-hospital mortality trends of infections among patients with cirrhosis: a nationwide study of hospitalised patients in the United States. Aliment Pharmacol Ther. 2014;40:105–112.

    CAS  Article  Google Scholar 

  14. 14.

    Project HCaU. National Inpatient Sample. Agency for Healthcare Research and Quality. https://www.hcup-us.ahrq.gov/nisoverview.jsp. Accessed Aug 8, 2018.

  15. 15.

    Schmidt ML, Barritt AS, Orman ES, Hayashi PH. Decreasing mortality among patients hospitalized with cirrhosis in the United States from 2002 through 2010. Gastroenterology. 2015;148(967–977):e962.

    Google Scholar 

  16. 16.

    Goldberg D, Ditah IC, Saeian K, et al. Changes in the prevalence of Hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterology. 2017;152(1090–1099):e1091.

    Google Scholar 

  17. 17.

    Younossi ZM, Otgonsuren M, Henry L, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62:1723–1730.

    CAS  Article  Google Scholar 

  18. 18.

    Dubberke ER, Butler AM, Nyazee HA, et al. The impact of ICD-9-CM code rank order on the estimated prevalence of Clostridium difficile infections. Clin Infect Dis. 2011;53:20–25.

    Article  Google Scholar 

  19. 19.

    Quality AfHRa. Medical Expenditure Panel Survey: using appropriate price indices for analyses ofhealth care expenditures or income across multiple years. https://meps.ahrq.gov/about_meps/Price_Index.shtml. Accessed Aug 2018.

  20. 20.

    Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19:335–351.

    CAS  Article  Google Scholar 

  21. 21.

    Ghantoji SS, Sail K, Lairson DR, DuPont HL, Garey KW. Economic healthcare costs of Clostridium difficile infection: a systematic review. J Hosp Infect. 2010;74:309–318.

    CAS  Article  Google Scholar 

  22. 22.

    Tandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis. Semin Liver Dis. 2008;28:26–42.

    CAS  Article  Google Scholar 

  23. 23.

    European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–460.

    Article  Google Scholar 

  24. 24.

    Garcia-Tsao G, Surawicz CM. Editorial: Clostridium difficile infection: yet another predictor of poor outcome in cirrhosis. Am J Gastroenterol. 2010;105:114–116.

    Article  Google Scholar 

  25. 25.

    Microbiology. ASf. A Practical Guidance Document for the Laboratory Detection of Toxigenic Clostridium difficile. Available at: https://apic.org/Resource_/TinyMceFileManager/Practice_Guidance/cdiff/ASM_Guidance_for_Laboratory_Detection.pdf. Accessed November 2019. 2010.

  26. 26.

    Cohen J, Limbago B, Dumyati G, et al. Impact of changes in Clostridium difficile testing practices on stool rejection policies and C. difficile positivity rates across multiple laboratories in the United States. J Clin Microbiol. 2014;52:632–634.

    Article  Google Scholar 

  27. 27.

    Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294:2989–2995.

    CAS  Article  Google Scholar 

  28. 28.

    Dubberke ER, Reske KA, McDonald LC, Fraser VJ. ICD-9 codes and surveillance for Clostridium difficile-associated disease. Emerg Infect Dis. 2006;12:1576–1579.

    Article  Google Scholar 

Download references

Funding

None.

Author information

Affiliations

Authors

Contributions

DK developed the study concept and design and was involved in acquisition, analysis, and interpretation of data. He developed the manuscript outline, obtained input from co-authors and drafted the manuscript. ERY, AAL, SPT, and GC were involved in interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. AA was involved in developing the study concept and design, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and study supervision.

Corresponding author

Correspondence to Donghee Kim.

Ethics declarations

Conflict of interest

Nothing to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10620_2020_6162_MOESM1_ESM.docx

Supplementary material 1 (DOCX 37 kb)

10620_2020_6162_MOESM2_ESM.tif

Supplementary material 2 (TIFF 1030 kb)

10620_2020_6162_MOESM3_ESM.tif

Supplementary material 3 (TIFF 1030 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kim, D., Yoo, E.R., Li, A.A. et al. Trends in Hospitalizations for Clostridioides difficile Infection in End-Stage Liver Disease, 2005–2014. Dig Dis Sci 66, 296–307 (2021). https://doi.org/10.1007/s10620-020-06162-0

Download citation

Keywords

  • Cirrhosis
  • National Inpatient Sample
  • Infection
  • Mortality