Trends in the Incidence and Outcomes ofClostridium difficileColitis in Hospitalized Cirrhotic Patients With Hepatic Encephalopathy: Nationwide Analysis 2002-2014

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Introduction: Clostridium difficile Infection (CDI) is rising both in incidence and severity during the last two decades worldwide. Patients with liver cirrhosis are at an increased risk for developing CDI because of frequent and prolonged hospitalizations, multiple comorbidities, antibiotics and PPI use. There is currently limited data that assesses the national disease burden and outcomes of CDI in cirrhotic patients with hepatic encephalopathy.

Methods: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of Hepatic Encephalopathy (HE) and Liver cirrhosis with or without C. diff colitis (ICD-9 codes 572.2, 571.2, 571.5, 571.6 & 008.45) as primary or secondary diagnosis during the period from 2002-2014. All analyses were performed with the use of PROC SURVEYMEANS, FREQUENCY and SURVEYLO-GISTIC procedures of SAS, version 9.4 (SAS Institute).

Results: From 2002-2014 there were total 17745 discharges of HE & Liver cirrhosis patients with C diff. colitis. Most of the patients were Caucasians (63.1%) with age 50-65 (48.8%), slight male predominance (55.9 %) and 0 to 3 co-morbid conditions (98.1%). There was a progressive rise in incidence and mortality of CDI in this cohort since 2008 (Figure 1). The median length of stay showed a slight decrease and the median cost of care showed a rise over 13 years. The overall mortality (17.9 vs 11.8%), Length of Stay > 5 days (76.5% Vs 44.4%) and discharge to SNF (35.8% Vs 22.1%) was significantly more in this cohort with C. Diff vs without C. Diff. Age above 50 years, biliary cirrhosis, spontaneous bacterial peritonitis and hepato-renal syndrome were significant predictors of mortality on multivariate logistic regression.

Figure: Graph Showing trends in Mortality, incidence, Median Length of Stay & Median Cost.

Conclusion: HE is the second most major frequent complication in cirrhosis following ascites. This study is the first one to assess the national burden of CDI in patients with HE & Cirrhosis. Diarrhea in these patients may represent a side-effect of the therapy used for HE, mostly lactulose, and this may lead to under-testing for C. difficile and thus to the worsening of underlying disease mainly due to the lack or delay in diagnosis of CDI in some cases and thus is an explanation for rising incidence and mortality. Clinicians should have high index of suspicion while evaluating these patients with diarrhea, in order to rapidly diagnose and treat this infection.

Table: Demographics & Basic Characteristics of Cirrhotic Patients with Hepatic Encephalopathy.

Table: Univariate and Multivariate regression analysis for predictors of C. diff colitis in Cirrhotic Patients with Hepatic Encephalopathy & Mortality in Cirrhotic patients with HE.