Impact of liver cirrhosis on morbidity and mortality of patients admitted to the hospital with necrotizing fasciitis

Abstract

BACKGROUND

Necrotizing fasciitis (NF) is a potentially fatal bacterial infection of the soft tissues. Liver cirrhosis appears to be a contributing factor to higher morbidity and mortality in patients with NF. This research article explores the relationship between these two conditions.

AIM

To evaluate whether liver cirrhosis increases morbidity and mortality in patients with NF, focusing on inpatient mortality, septic shock, length of stay, and hospital costs.

METHODS

This retrospective cohort study utilized data from the Healthcare Cost and Utilization Project 2019 National Inpatient Sample. Cases were identified as patients with both NF and cirrhosis, while controls were non-cirrhotic. The study focused on inpatient mortality as the primary outcome, with secondary outcomes including surgical limb amputation, mechanical ventilation rates, septic shock, length of stay, and hospital costs.

RESULTS

A total of 14920 patients were admitted to the hospital for management of NF, of which 2.11% had liver cirrhosis. Inpatient mortality was higher in cirrhotic patients (9.5% vs 3%; adjusted odds ratio = 3.78; P value = 0.02). Cirrhotic patients also had higher rates of septic shock (10.5% vs 4.9%, P value < 0.01). Length of hospital stay, total charges, and rates of mechanical ventilation were not statistically different between groups.

CONCLUSION

Liver cirrhosis is an independent risk factor of in-hospital mortality and morbidity in patients with NF. Clinicians should be aware of this association to ensure better clinical outcomes and spare healthcare expenditure.

Key Words: Necrotizing fasciitis; Cirrhosis; Mortality; Septic shock; Hospital charges

Core Tip: This study highlights liver cirrhosis as an independent risk factor contributing to increased mortality and morbidity in patients with necrotizing fasciitis. Patients with cirrhosis who develop necrotizing fasciitis experience markedly higher rates of inpatient mortality and septic shock compared to those without cirrhosis. These findings emphasize the critical need for clinicians to identify and address this association early, aiming to optimize management strategies and improve overall patient outcomes in this vulnerable population.

INTRODUCTION

Necrotizing fasciitis (NF), often known as “flesh-eating disease”, is a rapidly progressing bacterial infection of the soft tissues. This condition can quickly lead to severe damage to the skin, muscles, and underlying tissue and poses significant risks to patients and healthcare systems due to its high mortality rate and economic burden[1]. NF typically affects individuals with predisposing factors, including immunocompromised state, diabetes, renal failure, advanced age, malignancy, peripheral vascular disease, and obesity[2]. Liver cirrhosis impairs immune function and exacerbates systemic inflammation, potentially increasing infection susceptibility. Infections are observed in 25%-35% of hospitalized patients with cirrhosis, and in as many as 50% of those experiencing gastrointestinal bleeding - a rate 4 to 5 times higher than that seen in the general hospitalized population[3]. Given these effects, this study aims to investigate whether liver cirrhosis predisposes patients with NF to adverse outcomes, specifically its association with inpatient mortality and morbidity.

MATERIALS AND METHODS

The study sample was derived from the Healthcare Cost and Utilization Project National Inpatient Sample (NIS), which features inpatient data from 2019. The NIS is the largest publicly available inpatient healthcare in the United States. The NIS includes more than 7 million inpatient hospital records from 47 states and the district of Columbia, representing nearly 97% of the United States population. The NIS contains information on all hospital stays. The large size of the NIS enables researchers and policymakers to identify, track, and analyze national trends in healthcare utilization, access, charges, quality, and outcomes.

Analysis was conducted for all patients above 18 years of age with a principal inpatient diagnosis of NF defined by the International Classification of Diseases-10 code M72.6. We then divided these subjects into patients with cirrhosis, defined by the International Classification of Diseases-10 codes from K74, and those without cirrhosis. Further, they were analyzed based on demographics such as age, race, gender, insurance type, and the Charlson comorbidity index. Individuals included were compared for various comorbidities, including sepsis, systemic hypertension, diabetes mellitus, obesity, chronic kidney disease, chronic obstructive pulmonary disease, chronic heart failure, coronary artery disease, smoking status, alcohol use disorder, and gastroesophageal reflux disease. These variables were selected after a literature review of factors influencing the outcomes of patients with cirrhosis admitted with severe skin and soft tissue infections[4].

We reported the primary outcome from the data as in-hospital mortality, whereas secondary outcomes were surgical limb amputation, septic shock, length of stay, and hospital costs. We compared the outcomes between the two groups using χ²-tests and adjusted odds ratio through multivariate logistic regression analysis. A two-tailed P value of less than 0.05 is used for statistical significance.

RESULTS

A total of 14920 patients admitted to the hospital with NF were included in this study and divided into two groups. Of the total 14920 patients included in this study, 315 had liver cirrhosis, and 14605 did not have liver cirrhosis. Table 1 represents the differences in demographic characteristics of these two groups, including age, sex, Charlson comorbidity index score, insurance type, and comorbidities. The mean age was similar in cirrhotic (52.3 years old) and non-cirrhotic (52.7 years old) groups. The majority of patients in the cirrhosis group were male (85 % vs 15%, P value = 0.03). A score of 3 or greater on the Charlson comorbidity index was significantly more prevalent in patients with cirrhosis (57% vs 29%, P value < 0.01). We found clinically significant differences in the following comorbidities between the two groups: Diabetes mellitus type II (55% vs 40%, P value = 0.015), chronic kidney disease (25% vs 13%, P value < 0.01), and alcohol use disorder (24% vs 3%, P value < 0.01). Regarding insurance type and race, there were no significant differences between the two groups (Table 1). Patients with liver cirrhosis admitted for NF had a higher in-hospital mortality rate (9.5%) compared to non-cirrhotic patients (3%; adjusted odds ratio = 3.78; P value = 0.02) (Table 2). Although cirrhotic patients also experienced higher rates of septic shock, limb amputation, longer hospital stays, and increased total hospital charges, these differences were not statistically significant (Tables 2 and 3).

Table 1 Baseline demographic and clinical characteristics, n (%).

Characteristics	Without cirrhosis	With cirrhosis	P value
Total	14605 (98)	315 (2)
Female	6718 (85)	104 (15)	0.03
Mean age, years	52.7	52.3
Charlson comorbidity index score			< 0.01
0	3651 (25)	0 (0)
1	3943 (27)	69 (22)
2	2774 (19)	66 (21)
≥ 3	4235 (29)	179 (57)
Insurance type			0.73
Medicare	4673 (32)	94 (30)
Medicaid	4527 (31)	116 (37)
Private insurance	3943 (27)	81 (26)
Self-pay	1460 (10)	22 (7)
Comorbidities
Sepsis	2190 (15)	69 (22)	0.14
Diabetes mellitus	8032 (40)	126 (55)	0.015
Hypertension	8470 (58)	176 (56)	0.67
Obesity	5257 (36)	110 (35)	0.88
Chronic kidney disease	1898 (13)	78 (25)	< 0.01
Alcohol use disorder	438 (3)	75 (24)	< 0.01
Chronic obstructive pulmonary disease	1460 (10)	53 (17)	0.5
Chronic heart failure	730 (5)	9 (3)	0.45
Coronary artery disease	1898 (13)	40 (13)	0.38
Gastroesophageal reflux disease	1898 (13)	53 (17)	0.38
Cigarette smoking	4089 (28)	113 (36)	0.13

Table 2 Primary and secondary in-hospital outcomes of cirrhotic vs non-cirrhotic patients, n (%).

Total	Without cirrhosis	With cirrhosis	P value	Adjusted odds ratio1	P value	Confidence interval
In-hospital mortality rates and odds
460 (3)	430 (3)	30 (9.5)	< 0.01	3.78	0.02	1.23-11.5
In-hospital septic shock rates and odds
200 (5)	715 (4.9)	33 (10.5)	0.26	25.6	< 0.01	4.13-159.4
In-hospital surgical amputation rates and odds
1105 (7.4)	1066 (7.3)	30 (9.5)	0.5	1.15	0.77	0.43-3.08

¹Adjusted for age, sex, race, Charlson comorbidity index, insurance status, sepsis, hypertension, obesity, chronic kidney disease, chronic obstructive pulmonary disease, asthma, coronary artery disease, chronic heart failure, smoking status, dementia, supraventricular tachycardia, current long-term insulin use, and gastroesophageal reflux disease.

Table 3 In hospital lengths of stay and charges in cirrhotic vs non-cirrhotic patients.

Without cirrhosis	With cirrhosis	Adjusted means	P value
Length of stay means and adjusted means, days1
12.2	16.8	1.11	0.5
Total charges and adjusted means, dollars
152169	237775	46152	0.29

¹Adjusted for age, sex, race, Charlson comorbidity index, insurance status, sepsis, hypertension, obesity, chronic kidney disease, chronic obstructive pulmonary disease, asthma, coronary artery disease, chronic heart failure, smoking status, dementia, supraventricular tachycardia, current long-term insulin use, and gastroesophageal reflux disease.

DISCUSSION

Despite advancements in our understanding of NF, morbidity, and mortality associated with infections, particularly NF, as demonstrated in this report, remain high. Delayed diagnosis and the complexity of therapeutic interventions contribute to these outcomes, with treatment almost invariably requiring surgical debridement, necrosectomy, or fasciotomy[5]. While this condition is almost invariably associated with other predisposing factors, particularly an immunocompromised state[6], this study underlines cirrhosis as another factor that has not been previously highlighted as contributing, with higher mortality, worse septic state, and a resultant economic burden.

Cirrhotic patients hospitalized for NF not only exhibit poorer outcomes, as previously demonstrated, but they also have an increased risk of developing the condition, even in the absence of an identifiable skin wound or injury[7]. It is thought that bacteremia is favored in cirrhotic patients by a disrupted intestinal portal route, escaping phagocytosis by the liver reticuloendothelial system, which allows bacteria to translocate hematogenous and deposit in edematous soft tissues, leading to NF[8]. While the majority of NF cases are polymicrobial, known as type I[9], it seems that cirrhosis predisposes to monomicrobial infection, known as type III, particularly with gram-negative bacteria, i.e., Aeromonas, Klebsiella and Vibrio species[10], guiding toward a stewarded choice in antibiotic therapy in this subset of patients[11].

Mortality in patients admitted with NF has been found in multiple studies to be higher in cirrhotic patients vs non-cirrhotic, and our study replicated the latter finding. Mortality risk ranged across studies from 2.36 to 9.7[12,13], and it is hypothesized that it is related to a dyssynergy in systemic inflammation even in the absence of acute cirrhotic decompensation, with functional paralysis of immune cells and disrupted gut- liver axis[11,14,15]. The severity of liver disease seems to be also key in determining mortality, as a worse Child-Pugh grade, hypoalbuminemia, prolonged prothrombin time, and severe thrombocytopenia did correlate with mortality[11,15]. Certain comorbidities, if present, were also found to be independent risk factors of increased mortality in cirrhotic patients, such as advanced age, diabetes mellitus, heart failure, and acute kidney injury[16]. In the conducted study, the authors accounted for these variables in the regression analysis to control for potential confounding factors and subsequently determined that cirrhosis exhibited a distinct, elevated influence on mortality in patients with NF.

Our study was not the first to demonstrate that hospital charges are higher in patients with NF and cirrhosis, as Oud et al[16] revealed that hospital stay tends to be longer in these patients, making it at a certain period the costliest state hospital diagnosis. This study is not without limitations. The results and conclusions drawn are made under the assumption that the hospitals included in the analysis are representative of the general United States population. The analysis also depends on accurate coding by the hospitals involved, given that our results are derived from the International Classification of Diseases, tenth revision coding found in the database. Also, we could not account for all confounding biases that may have influenced desired outcomes. Additionally, the dataset’s limitations prevented us from accounting for or adjusting the severity of NF using validated scores like the Acute Physiology and Chronic Health Evaluation score. We attempt to mitigate this limitation by recognizing and adjusting for the occurrence of sepsis. Similarly, we were unable to classify baseline cirrhosis severity using the Child-Pugh score, which is crucial, as patients with varying stages of cirrhosis may experience different outcomes in severe infections like NF.

CONCLUSION

NF still poses a major problem in healthcare today, an issue that is accentuated in patients with cirrhosis. A better understanding of the correlation between these two entities is paramount for better resource allocation and optimal patient care.