Impact of Non-Alcoholic Fatty Liver Disease on Sepsis Inpatient Outcomes: A Nationwide Sample Analysis (2000-2019)

Abstract

Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD's impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07-1.32), higher odds of developing septic shock, and higher likelihood of development of multi-organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes.

Keywords: NAFLD; NASH; National Inpatient Sample; cirrhosis; epidemiology; inpatient all–cause mortality; non-alcoholic steatohepatitis; non–alcoholic fatty liver disease; observational study; sepsis.

Figure 1

Total discharge numbers, sepsis case numbers, concurrent NAFLD case numbers, and percentages from 2000 to 2019 in the United States, with regional analysis. (a) Sepsis cases and the percentage of sepsis cases among total hospital discharges have steadily increased from 311,650 cases, 0.9% in 2000, to 2,274,200 cases, 6.4% among total discharges in 2019. (b) The number of sepsis patients with concurrent NAFLD and the percentage of NAFLD among total sepsis admissions trended up steadily, increasing from 3759 cases, 1.2% of sepsis inpatients in the year 2000, to 94,525 cases, 4.2% of sepsis inpatients in the year 2019. (c) The number of sepsis patients and concurrent NAFLD case numbers also trended up in the four geographic regions of the United States during the twenty-year study period. (d) The percentage of NAFLD among sepsis admissions also trended up steadily in the four geographic regions of the United States, and the West persistently had the highest prevalence of NAFLD among sepsis patients. NAFLD—Non-Alcoholic Fatty Liver Disease.

Figure 2

Trend of adjusted in-hospital all-cause mortality rate of sepsis patients, with and without NAFLD, from 2000–2019, in the United States, with regional analysis. (a) The in-hospital all-cause mortality for sepsis admissions had trended down steadily, declining from 16.3% in the year 2000 to 9.1% in the year 2019. Similar trends were observed for both the NAFLD group (1.1% to 12.2%) (p-value < 0.001 for trend) and non-NAFLD group (16.2% to 9.1%) patients. The mortality rates in the sepsis-NAFLD group patients were persistently higher than those in the non-NAFLD counterparts (p < 0.001). (b) Similar trends of mortality were also observed in the regional analysis involving the four geographic regions of the United States in NAFLD-sepsis patients (Northeast, Midwest, South, and West), with the Northeast persistently having the highest sepsis mortality rate during the twenty-year study period. NAFLD—Non-Alcoholic Fatty Liver Disease.

Figure 3

Forrest plot showing clinical outcomes in sepsis admissions with and without NAFLD. Sepsis-NAFLD group patients had higher all-cause mortality and higher odds of developing cardiovascular dysfunction, hepatic dysfunction, renal dysfunction requiring hemodialysis, hematological dysfunction, and metabolic dysfunction. They also had higher odds of developing septic shock as compared to sepsis without NAFLD counterparts. OR and 95% CI were reported for outcome variables. The edges of the diamond point represent the 95% confidence interval limit. The graphical representation in the figure refers to the statistics in Table 2. NAFLD—Non-Alcoholic Fatty liver Disease; OR—Odds ratio; CI—confidence interval.

Figure 4

Trends of Adjusted In-Hospital Length of Stay of Sepsis Patients who died in the hospital, with and without NAFLD from 2000 to 2019 in the United States. From the year 2000 to the year 2019, the overall length of stay for sepsis patients who died in the hospital declined from 8.1 days in 2000 to 6.6 days in 2019. Similar trends were observed for both NAFLD (7.1 days to 5.8 days) and non-NAFLD groups (8.1 days to 6.7 days) patients. The length of stay in the sepsis-NAFLD group patients was persistently lower than their non-NAFLD counterparts (p < 0.001). NAFLD—Non-Alcoholic Fatty Liver Disease.