Epidemiological Trend of Sepsis in Patients with Hospital Admissions Related to Hepatitis C in Spain (2000-2015): A Nationwide Study

Abstract

Background: Hepatitis C virus (HCV) infection predisposes patients to other infectious diseases, such as sepsis. We aimed to analyze epidemiological trends of sepsis-related admissions, deaths, and costs in hospital admissions with chronic hepatitis C who had a hospital admission in Spain.

Methods: We performed a retrospective study of all hospitalizations involving chronic hepatitis C in the Spanish Minimum Basic Data Set (MBDS) between 2000 and 2015. This period was divided into four calendar periods (2000-2004, 2005-2007, 2008-2011, and 2012-2015).

Results: We selected 868,523 hospital admissions of patients with chronic hepatitis C over 16 years in the Spanish MBDS. Among them, we found 70,976 (8.17%) hospital admissions of patients who developed sepsis, of which 13,915 (19.61%) died during admission. We found an upward trend, from 2000-2003 to 2012-2015, in the rate of sepsis-related admission (from 6.18% to 10.64%; p < 0.001), the risk of sepsis-related admission (from 1.31 to 1.55; p < 0.001), and the sepsis-related cost per hospital admission (from 7198€ to above 9497€; p < 0.001). However, we found a downward trend during the same study period in the sepsis case-fatality rate (from 21.99% to 18.16%; p < 0.001), the risk of sepsis-related death (from 0.81 to 0.56; p < 0.001), and the length of hospital stay (LOHS) (from 16.9 to 13.9; p < 0.001). Moreover, the rate of bacterial Gram-positive and candidiasis infections decreased, while Gram-negative microorganisms increased from 2000-2003 to 2012-2015.

Conclusions: Sepsis, in chronic hepatitis C patients admitted to the hospital, has increased the period 2000-2015 and has been an increasing burden for the Spanish public health system. However, there has also been a significant reduction in lethality and LOHS during the study period. In addition, the most prevalent specific microorganisms have also changed in this period.

Keywords: epidemiology; hepatitis C; hospital admission; hospital resources; mortality; sepsis.

Figure 1

Summary of the relationship among hepatitis C infection, cirrhosis, immune system, bacterial infection, and sepsis. Abbreviations: HCC, hepatocellular carcinoma; LT, liver transplantation; NK, natural killer.

Figure 2

Flow chart of the selection of hospital admissions, who were included in this study, with chronic hepatitis C and sepsis in Spain (1997 to 2014).

Figure 3

Temporal trend of the sepsis rate (regarding all hospital admissions with a diagnosis of chronic HCV infection, %) and the sepsis-related death (regarding chronic HCV-infected patients with (A) hospital admission and sepsis, (B) CFR, %) in Spain (2000–2015). Statistic: Values were expressed as percentages. The Extended Mantel Haenszel Chi-Square was used to calculate the linear trend from 2000–2003 to 2012–2015. Abbreviations: HCV, hepatitis C virus; CFR, case-fatality rate.

Figure 4

Temporal trend of the risk of sepsis (regarding all hospital admissions with a diagnosis of chronic HCV infection) and the risk of sepsis-related death (regarding chronic HCV-infected patients with hospital admission and sepsis) in Spain (2000–2015). Statistic: Values were expressed as odds ratios (OR) and 95% of confidence intervals (95%CI). p-values were calculated by logistic regression analysis. Abbreviations: HCV, hepatitis C virus; aOR, adjusted odds ratio; 95% CI, 95% confidence interval.

Figure 5

Temporal trend of (A) the length of hospital stay and (B,C) the cost in hospital admissions of patients chronic hepatitis C and sepsis in Spain (2000–2015). Statistic: Values expressed as mean [95% Confidence Interval (CI)]. The linear trend, from 2000–2003 to 2012–2015, was calculated by the Mann–Kendall Trend Test. Abbreviations: HCV, hepatitis C virus.

Figure 6

Temporal trend of microorganism specific rate (not including unknown) linked to sepsis and sepsis-related death in hospital admissions of patients with chronic hepatitis C and sepsis in Spain (2000–2015). (A1): Sepsis-related admission with diagnosis of Gram-positive (+); (A2): Sepsis-related death with diagnosis of Gram-positive (+); (B1) Sepsis-related admission with diagnosis of Gram-negative (−); (B2) Sepsis-related death with diagnosis of Gram-negative (−); (C1) Sepsis-related admission with diagnosis of candidiasis; (C2) Sepsis-related death with diagnosis of candidiasis. Statistic: Values were expressed as percentages. The Extended Mantel Haenszel Chi-Square was used to calculate the linear trend from 2000–2003 to 2012–2015. Abbreviations: HCV, hepatitis C virus.