Risk Factors and Predictive Value of Sepsis in Patients with Liver Abscess

Introduction

Liver abscess (LA) is a common intra-abdominal infectious disease, and its incidence has increased in recent years. Despite advances in antimicrobial therapy and image-guided drainage techniques, a proportion of patients still progress to sepsis. Sepsis can lead to multiple organ dysfunction and death, substantially increasing disease burden and adversely affecting clinical outcomes.¹ Epidemiological studies indicate that pyogenic liver abscess (PLA) remains associated with substantial morbidity and mortality. The reported mortality of PLA ranges from 2.8% to 10.8%, and may exceed 20% among critically ill patients who develop sepsis or require intensive care.² Therefore, the early identification of high-risk patients is of considerable clinical importance. However, several challenges remain in the early recognition of sepsis in patients with LA. On the one hand, the clinical manifestations of LA-associated sepsis are often nonspecific and may be difficult to distinguish from worsening local infection or systemic inflammatory response syndrome.³ On the other hand, currently available assessment tools are largely derived from general sepsis populations and lack specificity for patients with LA, resulting in delayed diagnosis and risk stratification and potentially missing the optimal window for intervention.⁴

Previous studies have suggested that inflammatory responses, hepatic and renal dysfunction, and coagulation abnormalities may contribute to the development and progression of sepsis in patients with LA.^5,6 Severe infection can induce hepatocellular injury, cholestasis, renal hypoperfusion, and acute kidney injury, accompanied by activation of the coagulation cascade and increased platelet consumption. These pathophysiological changes not only reflect the impact of infection on multiple organ systems but may also provide important clues for the early identification of sepsis. Nevertheless, studies focusing on laboratory predictors and risk assessment of sepsis in patients with LA remain limited. Although several investigators have attempted to develop predictive models for sepsis in this population, these studies have generally been constrained by limited sample sizes, insufficient variable selection, and inadequate validation.⁷

Therefore, identifying factors associated with sepsis and establishing a simple and effective risk assessment tool for patients with LA remain clinically important. In the present study, we retrospectively analyzed the clinical data of 798 patients with LA to identify independent factors associated with sepsis and evaluate the predictive performance of relevant laboratory parameters and a combined prediction model. Our findings may facilitate early risk stratification and support individualized clinical management in patients with LA.

Subjects and Methods

Study Design and Participants

This single-center retrospective study included 798 patients with LA who were admitted to the General Hospital of Ningxia Medical University between January 2018 and December 2021.

The diagnosis of LA was established according to published criteria^8,9 and the following conditions: (1) the presence of clinical manifestations such as fever, chills, and right upper quadrant abdominal pain; (2) imaging findings on abdominal ultrasonography, contrast-enhanced computed tomography (CT), or magnetic resonance imaging (MRI) demonstrating one or more hepatic abscess lesions; and (3) positive microbiological culture results. For patients with negative microbiological findings, the diagnosis was confirmed by consensus of at least two attending physicians based on clinical, laboratory, and imaging findings.

The inclusion criteria were as follows: (1) fulfillment of the above diagnostic criteria for LA; (2) age ≥18 years; and (3) complete clinical data. The exclusion criteria were: (1) Malignancy; and (2) death on the day of admission (Figure 1).

Figure 1 Flowchart of patient selection.

Patients were classified into a sepsis group and a non-sepsis group according to the presence or absence of sepsis at admission. Sepsis was diagnosed according to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3),¹⁰ and was defined as an increase of ≥2 points in the Sequential Organ Failure Assessment (SOFA) score from baseline in the presence of infection.

This study was approved by the Ethics Committee of the General Hospital of Ningxia Medical University (Approval No. KYLL-2022-1204). The requirement for informed consent was waived owing to the retrospective nature of the study. All patient data were anonymized prior to analysis, and confidentiality was strictly maintained throughout the study. The study was conducted in accordance with the principles of the Declaration of Helsinki.

Data Collection

Clinical data obtained within 24 hours of admission and prior to the initiation of antimicrobial therapy or invasive procedures were collected. The collected variables included demographic characteristics, vital signs, comorbidities, clinical manifestations, laboratory findings, microbiological and imaging data, treatment information, disease severity scores, and prognostic outcomes.

Laboratory parameters included routine hematological and inflammatory indicators (WBC, NEUT%, PLT, and PCT); liver and renal function indicators (TBIL, ALT, albumin, BUN, and Cr); coagulation parameters (PT, APTT, and D-dimer); and electrolytes and other biochemical indicators (Na⁺, K⁺, Ca²⁺, blood glucose, and blood lactate).

Cases with missing key variables were excluded during the screening process, and no missing data were present in the final dataset included in the analysis.

Statistical Analysis

Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range [IQR]) according to their distribution. Between-group comparisons were performed using the independent-samples t-test or the Mann–Whitney U-test, as appropriate. Categorical variables were expressed as number (percentage) and were compared using the chi-square test or Fisher’s exact test.

Variables with P < 0.10 in the univariable analysis, together with clinically important variables, were entered into the multivariable logistic regression model. Forward stepwise regression was used to identify factors independently associated with sepsis, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.

ROC curve analysis was performed to evaluate the predictive performance of individual indicators and the combined model for sepsis in patients with liver abscess, and the area under the curve (AUC) was calculated. A two-sided P < 0.05 was considered statistically significant.

Results

Baseline Characteristics and Clinical Features

A total of 798 patients with LA were included, of whom 558 (69.9%) were classified into the sepsis group and 240 into the non-sepsis group. Compared with the non-sepsis group, patients in the sepsis group were younger and had a higher incidence of a history of hepatobiliary surgery and jaundice (P < 0.05; Table 1).

Table 1 Baseline Characteristics of Patients with and Without Sepsis

Laboratory Findings, Microbiological Characteristics, and Complications

As shown in Table 2, compared with the non-sepsis group, patients in the sepsis group exhibited significantly higher inflammatory marker levels and more severe liver, renal, and coagulation dysfunction (P < 0.05). Electrolyte disturbances and elevated blood lactate were also more common in septic patients (P < 0.05). The positive blood culture rate was significantly higher in the sepsis group (20.1% vs. 5.4%, P < 0.001). In addition, the incidences of major complications, including acute renal failure, MODS, pulmonary infection, hypoproteinemia, serous cavity effusion, and thrombosis, were significantly higher in patients with sepsis (all P < 0.05).

Table 2 Comparison of Laboratory Parameters, Etiological Characteristics, and Imaging Features Between the Two Groups of Patients

Treatment Strategies and Clinical Management

There were no statistically significant differences in treatment modalities between the two groups (P > 0.05), with antibiotic therapy combined with percutaneous catheter drainage being the main treatment approach in both groups. However, patients in the sepsis group received more intensive antibiotic therapy, including a higher proportion of combination therapy, a greater number of antibiotics, and a longer duration of treatment (P < 0.001). In addition, the classes of antibiotics used differed significantly between the two groups (P < 0.05; Table 3).

Table 3 Comparison of Treatment Modalities and Antibiotic Use Between the Two Groups

Comparison of Disease Severity and Clinical Outcomes

Compared with the non-sepsis group, patients in the sepsis group had significantly higher APACHE II and SOFA scores (P < 0.001), higher ICU admission rates, and more frequent use of organ support therapies, including mechanical ventilation, continuous renal replacement therapy (CRRT), and vasoactive agents (P < 0.05). In addition, the 28-day mortality rate was significantly higher in the sepsis group (P < 0.05; Table 4).

Table 4 Comparison of Disease Severity and Outcomes Between the Two Groups

Multivariate Analysis of Risk Factors for Sepsis

Multivariate logistic regression analysis demonstrated that a history of hepatobiliary surgery, elevated Cr and TBIL levels, and decreased PLT levels were independently associated with the development of sepsis in patients with liver abscess (P < 0.05; Table 5 and Figure 2).

Table 5 Univariable and Multivariable Logistic Regression Analyses of Factors Associated with Sepsis in Patients with Liver Abscess

Figure 2 Forest plot of multivariate logistic regression analysis for risk factors of sepsis in patients with liver abscess.

ROC Curve Analysis and Predictive Performance

ROC curve analysis demonstrated that TBIL, Cr, and PLT each showed significant predictive value for sepsis (P < 0.001). Furthermore, the combination of these three indicators achieved improved predictive performance, with an AUC of 0.848, indicating good discriminative ability (Table 6).

Table 6 ROC Curve Analysis of Predictive Models for Sepsis in Patients with Liver Abscess

Discussion

The present study showed that patients in the sepsis group were younger than those in the non-sepsis group, which is not entirely consistent with previous studies that have generally identified advanced age as a risk factor for sepsis.¹¹ This finding may be related to disease-specific characteristics and differences in host responses among patients with liver abscess. Previous studies have demonstrated that the development and progression of sepsis are closely associated with dysregulated host immune responses.¹² Some patients may develop an excessive inflammatory response during the early stage of infection, thereby accelerating disease progression. In addition, Klebsiella pneumoniae is one of the most common pathogens causing liver abscess and is characterized by strong invasiveness, frequently leading to bacteremia and metastatic infections. Such invasive infections have been reported to occur more commonly in relatively younger patients.^13,14 Therefore, younger age does not necessarily indicate a lower risk of sepsis among patients with liver abscess, and early risk assessment should not be overlooked in younger individuals in clinical practice.

In the present study, patients with sepsis exhibited more pronounced inflammatory responses, coagulation abnormalities, and multi-organ dysfunction, suggesting that liver abscess-related infection had progressed from a localized infection to a dysregulated systemic inflammatory response. The pathophysiology of sepsis involves complex interactions among inflammation, activation of the coagulation system, and microcirculatory dysfunction. Persistent release of inflammatory mediators can lead to endothelial injury and increased vascular permeability, while simultaneously activating coagulation pathways and suppressing fibrinolysis. These processes ultimately promote microthrombus formation, aggravate tissue hypoperfusion, and contribute to organ dysfunction.¹⁵ In our study, the sepsis group showed a significantly higher rate of positive blood cultures, suggesting that hematogenous dissemination of pathogens may play an important role in disease progression. In contrast, no significant differences were observed in imaging characteristics between the two groups, indicating that the occurrence of sepsis is not solely determined by local abscess features but is more closely related to systemic infection dissemination and host response status. These findings further support the concept that liver abscess-associated sepsis results from the combined effects of infection and dysregulated host responses.^16,17

We also found that patients with sepsis had significantly higher SOFA and APACHE II scores, as well as higher rates of ICU admission, greater requirements for organ support therapies, and increased 28-day mortality, indicating that sepsis substantially increases disease burden and adversely affects clinical outcomes in patients with liver abscess.¹⁸ Furthermore, multivariable logistic regression analysis demonstrated that a history of hepatobiliary surgery and elevated levels of TBIL and Cr were independent risk factors for sepsis, whereas lower PLT levels were independently associated with the occurrence of sepsis. Previous hepatobiliary surgery may alter the normal biliary anatomy and compromise local defense barriers, thereby increasing the risk of ascending bacterial infection and the spread of biliary tract infections, ultimately promoting the development of sepsis. Elevated TBIL reflects infection-related hepatic dysfunction and cholestasis. Previous studies have shown that hyperbilirubinemia is not only associated with sepsis severity but also serves as an important indicator of invasive infection and poor prognosis.^19,20 Acute kidney injury is one of the most common organ dysfunctions in sepsis and is closely associated with inflammation-mediated microcirculatory disturbances, renal hypoperfusion, and tubular injury.²¹ On the other hand, thrombocytopenia often reflects activation of inflammatory responses and coagulation dysfunction. Beyond serving as a marker of disease severity, activated platelets participate in immune regulation, endothelial injury, and microthrombus formation, thereby further aggravating organ dysfunction.²² Therefore, TBIL, Cr, and PLT reflect sepsis-related organ injury from the perspectives of hepatic function, renal function, and coagulation status, respectively, providing strong biological plausibility for their predictive value.

In recent years, most predictive models for sepsis have been developed based on inflammatory biomarkers, organ function parameters, or disease severity scores. However, studies specifically focusing on patients with liver abscess remain limited.⁵ In the present study, we developed a combined predictive model based on TBIL, Cr, and PLT. These indicators are routinely available from standard laboratory testing and do not require additional measurement of specialized biomarkers, making the model readily applicable for early risk assessment upon hospital admission. ROC curve analysis demonstrated that all three indicators individually possessed predictive value, with PLT showing relatively better discriminative performance, whereas Cr alone exhibited comparatively limited predictive ability. Notably, the combined model achieved an AUC of 0.848, indicating good discriminative performance. Since TBIL, Cr, and PLT reflect hepatic function, renal function, and coagulation status, respectively, their combined assessment may capture key pathophysiological changes occurring during the development of sepsis from multiple perspectives, thereby improving the identification of high-risk patients. Therefore, this model may provide a useful tool for early risk stratification and clinical management in patients with liver abscess.

Several limitations of this study should be acknowledged. First, this was a single-center retrospective study, which may be subject to selection bias and may limit the generalizability of the findings. Second, although multiple clinical variables were included and adjusted for in the multivariable analysis, residual confounding from unmeasured factors, such as prior antibiotic exposure and duration of infection before admission, cannot be completely excluded. Third, owing to the retrospective design, variations in clinical management among patients could not be fully controlled. In addition, external validation of the predictive model has not yet been performed, and its calibration and stability across different regions and healthcare settings remain to be determined. Therefore, future multicenter prospective studies are warranted to further validate our findings and assess the robustness and clinical applicability of the proposed predictive model.

Conclusion

In conclusion, a history of hepatobiliary surgery, elevated TBIL and Cr levels, and decreased PLT were independently associated with sepsis in patients with liver abscess. The predictive model based on TBIL, Cr, and PLT showed good discriminative performance and may facilitate early risk assessment, timely clinical intervention, and optimized management of high-risk patients. Nevertheless, external validation in prospective multicenter studies is required to confirm its generalizability and clinical utility.