Preoperative Nutritional Index as a Predictor of Pulmonary Infection and Mortality in Liver Transplant Patients

Introduction

Liver transplantation is a radical curative method for end-stage decompensated liver disease and malignancy, offering a significant improvement in liver function and overall survival. This procedure is vital for patients with liver disease, which is a major public health problem due to its high morbidity and mortality rates [1,2]. However, the prognosis for liver transplant recipients can be adversely affected by postoperative complications, which are often exacerbated by the long waiting times for transplantation and progression of the underlying disease [3].

Postoperative complications, particularly those related to the evolution of liver disease, can severely impact nutritional and functional status [4]. Studies have shown that malnutrition, prevalent in patients with end-stage liver disease due to insufficient hepatic synthesis, is associated with an increased risk of postoperative complications [5]. This underscores the need to assess and optimize nutritional status to improve outcomes preoperatively.

The prognostic nutritional index (PNI), calculated based on serum lymphocyte count and serum albumin level, is a well-established tool for assessing nutritional and inflammatory status, and it has been used to predict surgical risk in various conditions [6–8]. Previous research has demonstrated the utility of preoperative PNI in predicting prognosis for patients undergoing surgery for hepatocellular carcinoma, with significant correlations between PNI scores and both survival rates and postoperative complications [9–12].

Despite the established role of PNI in other surgical contexts, its prognostic value for patients undergoing deceased donor liver transplants, particularly in predicting postoperative pulmonary infections and in-hospital mortality, remains unclear. Addressing this knowledge gap is crucial, as these outcomes significantly affect patient recovery and long-term prognosis.

Therefore, the current study was performed to assess the predictive value of preoperative PNI for postoperative pulmonary infection and in-hospital mortality in patients who received a deceased donor liver transplant. This investigation aims to provide new insights that could enhance preoperative evaluation and postoperative management, ultimately improving patient outcomes in liver transplantation.

Material and Methods

STUDY DESIGN AND PATIENT POPULATION:

The current retrospective cohort study included 177 patients who received deceased donor liver transplants at our hospital from January 2020 to June 2021. The Research Ethics Committee of Third People’s Hospital of Shenzhen approved this study (approval no: 2022-037-02), and informed consent was waived by the committee of Third People’s Hospital of Shenzhen because of the retrospective nature of the study. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Patients were included if they met the following criteria: (1) available serum lymphocyte and albumin level results and preoperative PNI results; and (2) end-stage decompensated liver disease or malignancy and reception of a deceased donor liver transplant.

DATA COLLECTION AND OUTCOME DEFINITION:

All demographic and clinical data were extracted from electronic medical records, including sex, age, body mass index (BMI) (divided into: underweight <18.0 kg/m2; normal: 18.0–23.0 kg/m2; overweight: >23.0 kg/m2), liver cirrhosis, tumors of the liver, liver failure, model for end-stage liver disease (MELD) score, Child–Pugh score, alpha fetoprotein (AFP), and PNI. The calculations of MELD [12] and PNI were referencing previous studies [13,14]. The cut-off value of PNI was 40, and patients were divided into normal (≥40) and low PNI (<40) groups [15,16]. The variables required to calculate the preoperative PNI score were collected within one week prior to surgery. The outcomes investigated included postoperative pulmonary infection and in-hospital mortality. Postoperative pulmonary infection was diagnosed based on imaging evidence of interstitial lung changes or patchy shadows, confirmed by positive sputum cultures, and post-surgical lung examination revealing abnormal inflammatory breath sounds. In-hospital mortality was defined as death occurring in the hospital.

STATISTICAL ANALYSIS:

Continuous variables were first tested for normality, and then presented as means±standard deviations (for normally distributed data) or medians (interquartile ranges) (for non-normally distributed data), with between-group comparisons conducted using independent samples t-tests (for normally distributed data) and Kruskal-Wallis H tests (for non-normally distributed data). Categorical variables were expressed as counts and frequencies, with group differences assessed by Chi-square tests. Univariate logistic regression was applied to identify potential predictors of postoperative pulmonary infection and in-hospital mortality, and the variables were subjected to multivariate analyses using stepwise selection at α=0.05 and β=0.10. A receiver operating characteristic (ROC) curve was created based on multivariate logistic regression analysis, and the predictive value was assessed using the area under the curve (AUC). Statistical significance was defined as a two-tailed P<0.05. All statistical analyses were performed using SPSS Version 19.0 for Windows (SPSS, Chicago, IL, USA).

Results

BASELINE CHARACTERISTICS OF INCLUDED PATIENTS:

The baseline characteristics of the enrolled patients are shown in Table 1. Of the 177 included patients, the median age was 49.00 (40.00, 57.00) years, and 81.92% (145/177) of the patients were male. The primary reasons for liver transplantation were liver cirrhosis, tumors of livers, and liver failure, and the proportion of included patients were 75.14%, 37.29%, and 31.07%, respectively. There were significant differences between patients with low and normal PNI in terms of age (P=0.011), BMI group (P=0.023), liver cirrhosis (P=0.025), liver tumors (P=0.022), MELD score (P=0.004), and Child–Pugh score (P=0.001), whereas no significant differences were observed between groups for sex (P=0.501), BMI (P=0.065), liver failure (P=0.167), and AFP (P=0.970). Moreover, the incidence of postoperative pulmonary infection (P<0.001) and in-hospital mortality (P=0.011) in patients with low PNI was significantly higher than that in patients with normal PNI.

POSTOPERATIVE PULMONARY INFECTION:

The results of the univariate analyses for postoperative pulmonary infection are shown in Table 2. A normal PNI was associated with a reduced risk of postoperative pulmonary infection compared with a low PNI (OR: 0.21; 95% CI: 0.09–0.49; P<0.001). After adjusting for potential confounding factors, we noted that normal PNI was associated with a reduced risk of postoperative pulmonary infection compared with low PNI (OR: 0.21; 95% CI: 0.09–0.49; P=0.001). The predictive value of preoperative PNI on subsequent postoperative pulmonary infection are shown in Figure 1, and the AUC was 0.66 (95% CI: 0.59–0.73).

IN-HOSPITAL MORTALITY:

The results of the univariate analyses for in-hospital mortality are shown in Table 2. Normal PNI was associated with a reduced risk of in-hospital mortality compared to low PNI (OR: 0.23; 95% CI: 0.08–0.70; P=0.011). Moreover, overweight was associated with a reduced risk of in-hospital mortality (OR: 0.17; 95% CI: 0.03–0.86; P=0.021). After adjusting for potential confounding factors, we noted normal PNI was associated with a reduced risk of in-hospital mortality (OR: 0.23; 95% CI: 0.08–0.70; P<0.001). The predictive value of preoperative PNI on in-hospital mortality are shown in Figure 2, and the AUC was 0.65 (95% CI: 0.56–0.73).

Discussion

LIMITATION:

This study has several limitations. Its retrospective design may have led to selection and recall biases. Post-transplant treatments, crucial for patient outcomes, were not considered. Patient health variations could be linked to PNI but were not uniformly analyzed. PNI scores may have been influenced by factors like hypersplenism, and non-nutritional reduction of circulating lymphocytes. The type of organisms in pulmonary infection and the specific type of pulmonary infection were not assessed. The risk of other infectious complications, including post-transplant sepsis, cholangitis, urinary tract infection, and intra-abdominal infection, were not available in most included patients, which should explore the prognostic role of PNI on post-transplant sepsis in patients after liver transplantation. Sensitivity and subgroup analyses according to patient characteristics were not performed because of the small number of included patients. Additionally, the predictive value of the preoperative PNI was not validated in an external cohort, so this requires further verification.

Conclusions

This study found that the preoperative PNI was significantly associated with postoperative pulmonary infection and in-hospital mortality in patients after liver transplantation, while the AUC of the preoperative PNI for postoperative pulmonary infection and in-hospital mortality were 0.66 (95% CI: 0.59–0.73) and 0.65 (95% CI: 0.56–0.73), respectively. Considering the small sample size of this study, further large-scale prospective studies are needed to validate the reliability of the constructed predictive model.