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28 December 2024: Database Analysis  

Liver Cirrhosis as a Predictor of Infection Risk in Patients Undergoing Ventriculoperitoneal Shunt Surgery: A Retrospective Cohort Analysis from the Taiwan National Health Insurance Research Database (NHIRD)

Yu-Chung Juan12ADEF, Hung-Lin Lin1ADF, Yu-hsiang Lin ORCID logo1ADF, Wen-Miin Liang3ACDG, Yu-Kai Cheng14DF, Yu-Jun Chang5DE, Chien-Tung Yang1DF, Der-Yang Cho1DF, Chun-Chung Chen126ADEF*

DOI: 10.12659/MSM.946745

Med Sci Monit 2024; 30:e946745

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Abstract

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BACKGROUND: Ventriculoperitoneal (VP) shunt surgery is a widely used procedure for managing hydrocephalus; however, postoperative infections remain a serious complication, increasing morbidity and mortality. Known risk factors include prior surgeries, steroid use, and concurrent procedures. However, the role of liver cirrhosis, a condition that compromises immune function and predisposes patients to infections, has not been fully investigated in the context of neurosurgery. Current literature lacks large-scale studies evaluating whether liver cirrhosis increases infection risk after VP shunt surgery. This study aims to address this gap using a nationally representative database, to compare the risk of postoperative infections in patients with and without liver cirrhosis following VP shunt surgery, utilizing data from the Taiwan National Health Insurance Research Database (NHIRD).

MATERIAL AND METHODS: A retrospective cohort study analyzed 1766 patients with and 37 995 patients without liver cirrhosis who underwent their first VP shunt surgery between January 2010 and December 2019. Infection risk was assessed at 6 months and 1 year after surgery. Additional factors, such as cerebral hemorrhage, aneurysm, brain tumors, decompressive craniectomy, and cranioplasty, were considered. Fine and Gray regression accounted for death as a competing risk.

RESULTS: After we adjusted for potential confounders, patients with cirrhosis showed a 1.41-fold increased risk of infection at 6 months (95% CI: 1.10-1.81, P=0.007) and 1.39-fold at 1 year (95% CI: 1.12-1.73, P=0.003) compared with patients without cirrhosis.

CONCLUSIONS: Liver cirrhosis significantly elevates infection risk following VP shunt surgery, highlighting the need for tailored perioperative strategies to improve outcomes for these patients.

Keywords: Liver Cirrhosis, Ventriculoperitoneal Shunt, infections, Meningitis

Introduction

Ventriculoperitoneal (VP) shunting is a critical neurosurgical procedure that mitigates the effects of hydrocephalus by diverting cerebrospinal fluid from the cerebral ventricles to the peritoneal cavity. This intervention is essential for relieving increased intracranial pressure and its associated neurological symptoms. While VP shunting is deemed effective, it harbors a substantial risk of complications, notably infection. Studies suggest that the postoperative infection rates can vary widely, typically between 5% and 15%, influenced by factors such as patient comorbidities, surgical techniques, and the quality of postoperative care [1,2].

Liver cirrhosis, characterized by the progressive fibrosis and formation of scar tissue within the liver, leads to compromised immune function in patients. This is evidenced by decreased phagocytic activity of neutrophils and macrophages, along with lower levels of opsonizing antibodies, making them more susceptible to infections [3]. Kaltenbach and Mahmud further emphasize that patients with cirrhosis face significantly higher risks during and after surgery, due to impaired hepatic function, reduced immune responses, and altered coagulation processes [4]. These factors contribute to poor wound healing, increased susceptibility to infection, and other complications [5]. Given these compromised immune defenses, patients with liver cirrhosis represent a particularly vulnerable group for postoperative complications, including central nervous system infections following VP shunt procedures. This increased risk underscores the need for careful preoperative evaluation and enhanced infection control measures for these patients, to reduce morbidity and mortality [5,6].

Despite the recognized risks, there is a notable gap in the literature, specifically concerning the incidence and management of infections after VP shunt surgery among patients with cirrhosis. This gap is particularly concerning given the increasing prevalence of liver cirrhosis driven by factors like viral hepatitis and alcohol use, with significant geographic variations in incidence [7,8].

The primary focus of this study is to analyze the patient populations most susceptible to post-VP shunt infections, which can lead to severe central nervous system infections. The insertion of a VP shunt is indicated in cases of hydrocephalus, where it serves to divert excess cerebrospinal fluid from the ventricles to the peritoneal cavity, thereby alleviating intracranial pressure.

By comparing infection rates and clinical outcomes between patients with and without cirrhosis, this research seeks to identify specific risks and challenges that may influence perioperative care in this vulnerable population. Through these findings, the study aims to provide evidence-based insights that can guide clinical decision-making, optimize protocols for infection prevention, and ultimately enhance the management of hydrocephalus in patients with significant comorbidities, thereby contributing to improved clinical outcomes and quality of life for these individuals. The aims of this study are to assess the incidence and risk factors associated with postoperative infections following VP shunt surgery in patients with liver cirrhosis, using comprehensive data from the Taiwan National Health Insurance Research Database (NHIRD).

Material and Methods

DATA SOURCE:

Since 1995, Taiwan’s National Health Insurance (NHI) program has provided healthcare coverage to approximately 23 million residents. At its inception, the NHI program covered around 40% of the population. By 2008, coverage had reached 99.48%, and by 2010, it exceeded 99.9%. By 2021, the coverage rate surpassed 99% of the entire population. The NHIRD, published by the Department of Health and managed by the Bureau of National Health Insurance, offers comprehensive health data from 2008 to 2021. This data set, which covers over 23 475 000 individuals, includes anonymized secondary data released for research purposes, with high accuracy and completeness assured by the authorities. The NHIRD contains extensive health care information, including demographics, clinical visit dates, diagnostic codes, prescription records, and associated costs. Disease diagnoses were coded using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), and later the Tenth Revision, Clinical Modification (ICD-10-CM), across the study period. This study protocol was approved by the ethics committee at China Medical University and Hospital and followed the principles of the Declaration of Helsinki. The data was provided by the National Health Research Institutes and the Collaboration Center of Health Information Application under Taiwan’s Ministry of Health and Welfare, ensuring a comprehensive, population-wide resource for public health research.

PATIENT SELECTION:

This study utilized data from the NHIRD and included patients aged 18 years and older who underwent their first VP shunt surgery between January 1, 2010, and December 31, 2019. Initially, 57 201 patients were identified. After excluding 11 108 patients who did not undergo surgery within the specified period, 1590 patients under the age of 18 years, 4718 patients with a prior infection before the index date, and 24 patients with previous abdomen surgery, a total of 39 761 patients remained. These patients were categorized into 2 cohorts: those with a diagnosis of liver cirrhosis prior to the VP shunt procedure, referred to as the “liver cirrhosis cohort” (1766 patients), and those without a liver cirrhosis diagnosis, referred to as the “non-liver cirrhosis cohort” (37 995 patients). The date of the VP shunt surgery was designated as the index date for both cohorts. All patients were followed until they developed an infection, died, discontinued their insurance plan, or until December 31, 2021, whichever came first (Figure 1).

DEFINITION OF TREATMENT HISTORIES, MEDICATION AND COMORBIDITIES:

In this study, we also considered treatment histories, specifically focusing on treatments received on the index day for conditions, such as cerebral hemorrhage, aneurysms, brain tumors, intracranial decompression, and cranioplasty. Steroid use was defined as taking steroids for at least 30 days within the 3 months preceding the VP shunt surgery. External ventricular drainage during the same hospitalization was also included. History and concurrent intracranial surgeries during the same hospitalization, including cerebral hemorrhage, aneurysms, brain tumors, decompressive craniectomy, and cranioplasty, were evaluated. Comorbidities for both cohorts were recorded either prior to or on the index day, including diabetes mellitus, hypertension, congestive heart failure, end-stage renal disease, malnutrition, pneumonia, and urinary tract infections.

DEFINITION OF RESEARCH RESULTS:

The primary outcome was defined as the occurrence of central nervous system infections and surgical site infections within 6 and 12 months following VP shunt surgery. This included critical and life-threatening conditions, such as meningitis and brain abscess, which are significant causes of mortality.

STATISTICAL ANALYSIS:

The study began by examining baseline characteristics and comorbidities. Differences between the 2 cohorts were evaluated using the t test for continuous variables and chi-square tests for categorical variables. To evaluate the risk of infection, we accounted for death as a competing event, using the Fine and Gray regression hazards model, adjusted for age, sex, steroid use, external ventricular drainage, history of intracranial surgery, concurrent intracranial surgery during the same hospitalization, and comorbidities. The cumulative incidence of infection was determined using the Kaplan-Meier method, and differences between cohorts were tested with the log-rank test. To examine the robustness of the main findings, the liver cirrhosis cohort was matched 1: 10 with the non-liver cirrhosis cohort based on age, sex, steroid use, external ventricular drainage, history of intracranial surgery, concurrent intracranial surgery during the same hospitalization, and propensity scores for comorbidities. Data management and analyses were performed with Statistical Analysis System software for Windows (version 9.4; SAS Institute, Cary, NC, USA).

Results

BASELINE CHARACTERISTICS OF LIVER CIRRHOSIS AND NON-LIVER CIRRHOSIS COHORTS:

Patients who underwent VP shunt surgery were divided into 2 cohorts: the liver cirrhosis cohort, consisting of 1766 patients, and the non-liver cirrhosis cohort, consisting of 37 995 patients, identified from 2010 to 2019. Figure 1 details the selection process of study participants. The distributions of age, sex, steroid use, external ventricular drainage, history of intracranial surgery, concurrent intracranial surgery during the same hospitalization, comorbidities, and infection incidences were calculated and compared between the liver cirrhosis and non-liver cirrhosis cohorts (Table 1).

INFECTION INCIDENCE AND RISK INDICATORS:

Using the Fine and Gray regression hazards model, the study showed that the 6-month cumulative incidence of infection was 1.41 times higher in the liver cirrhosis cohort than in the non-liver cirrhosis cohort (95% CI: 1.27–1.56, P=0.007; Table 2). Also, several other indicators were associated with increased infection risk, including steroid use (subdistribution adjusted hazard ratio [sHR]=1.56, P<0.001), history of cerebral hemorrhage (sHR=1.48, P<0.001), intracranial decompression (sHR=1.37, P=0.018), concurrent cerebral hemorrhage during the same hospitalization (sHR=1.40, P<0.001), concurrent intracranial decompression (sHR=1.31, P=0.012), and cranioplasty (sHR=1.34, P=0.002). Compared with that in the non-liver cirrhosis cohort, the 1-year infection risk for the liver cirrhosis cohort was also significantly higher, with an sHR of 1.39 (95% CI: 1.12–1.73, P=0.003; Table 3). As shown in Tables 4 and 5, we compared the 2 matched cohorts and found that the 6-month cumulative incidence of infection was 1.49 times higher in the liver cirrhosis cohort than in the non-liver cirrhosis cohort (95% CI: 1.15–1.93, P=0.003). Additionally, the 1-year infection risk was 1.42 times higher (95% CI: 1.13–1.78, P=0.003). These tables demonstrate the robustness of the study’s results.

CUMULATIVE INCIDENCE OF INFECTION:

Cumulative incidence of infection was significantly higher in the liver cirrhosis cohort than in the non-liver cirrhosis (log-rank test P<0.0001), as shown in the Kaplan-Meier curves (Figure 2).

Discussion

STRENGTHS:

One of the key strengths of this study is the use of the NHIRD, which covers over 99% of Taiwan’s population. This comprehensive coverage ensures that nearly all patients who have undergone VP shunt surgery are included in the study, minimizing selection bias and enhancing the generalizability of the findings. The NHIRD’s extensive data on hospital admissions, surgical procedures, and long-term health outcomes allows for a robust analysis of infection risks in a real-world setting, providing valuable insights into the clinical management of patients with cirrhosis undergoing VP shunt surgery.

LIMITATIONS:

Despite its strengths, this study has several limitations. The retrospective design may have introduced biases related to data recording and coding in the NHIRD, potentially affecting the accuracy of documented conditions and treatments. Additionally, the absence of detailed clinical data, such as the severity of liver disease (eg, Child-Pugh score), limits the ability to perform more refined risk assessments [16]. The lack of perioperative care details, such as specific infection control measures or the types of shunt materials used, also affects the ability to evaluate their influence on infection outcomes. Furthermore, the study does not provide detailed information on the pathogens responsible for infections or their resistance profiles, limiting the ability to develop targeted antimicrobial strategies. There is also a potential for residual confounding due to unmeasured lifestyle factors, such as alcohol consumption, and concerns about the generalizability of the findings to populations outside of Taiwan. Lastly, the decade-long study period may not have accounted for changes in surgical practices, which could influence infection rates. Future research should focus on prospective studies that provide detailed clinical evaluations of patients with cirrhosis undergoing VP shunt surgery, including an exploration of the microbiological spectrum of infections to inform targeted therapies [17].

Conclusions

This study demonstrates that patients with liver cirrhosis undergoing VP shunt surgery face a significantly higher risk of postoperative infections, especially when additional neurological procedures are involved. These findings underscore the importance of tailored perioperative management and enhanced infection control measures, to improve outcomes and reduce complications in this high-risk group.

References

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2. Simon TD, Riva-Cambrin J, Srivastava R, Hospital care for children with hydrocephalus in the United States: Utilization, charges, comorbidities, and deaths: J Neurosurg Pediatr, 2008; 1(2); 131-37

3. Albillos A, Lario M, Álvarez-Mon M, Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance: J Hepatol, 2014; 61(6); 1385-96

4. Kaltenbach MG, Mahmud N, Assessing the risk of surgery in patients with cirrhosis: Hepatol Commun, 2023; 7(4); e0086

5. Sunderland GJ, Conroy EJ, Nelson A, Factors affecting ventriculoperitoneal shunt revision: A post hoc analysis of the British Antibiotic and Silver Impregnated Catheter Shunt multicenter randomized controlled trial: J Neurosurg, 2023; 138(2); 483-93

6. Pelegrín I, Lora-Tamayo J, Gómez-Junyent J, Management of ventriculoperitoneal shunt infections in adults: Analysis of risk factors associated with treatment failure: Clin Infect Dis, 2017; 64(8); 989-97

7. Scaglione S, Kliethermes S, Cao G, The epidemiology of cirrhosis in the United States: A population-based study: J Clin Gastroenterol, 2015; 49(8); 690-96

8. Lee WM, Hepatitis B virus infection: N Engl J Med, 1997; 337(24); 1733-45

9. Le Guillou-Guillemette H, Vallet S, Gaudy-Graffin C, Genetic diversity of the hepatitis C virus: impact and issues in the antiviral therapy: World J Gastroenterol, 2007; 13(17); 2416-26

10. Pellegris G, Ravagnani F, Notti P, B and C hepatitis viruses, HLA-DQ1 and -DR3 alleles and autoimmunity in patients with hepatocellular carcinoma: J Hepatol, 2002; 36(4); 521-26

11. Simon TD, Whitlock KB, Riva-Cambrin J, Association of intraventricular hemorrhage secondary to prematurity with cerebrospinal fluid shunt surgery in the first year following initial shunt placement: J Neurosurg Pediatr, 2012; 9(1); 54-63

12. Mioton LM, Jordan SW, Hanwright PJ, The relationship between preoperative wound classification and postoperative infection: A multi-institutional analysis of 15,289 patients: Arch Plast Surg, 2013; 40(5); 522-29

13. Kapoor JR, Myocarditis: N Engl J Med, 2009; 361(4); 422-23 author reply 423–24

14. Pollock BE, Jacob JT, Brown PD, Nippoldt TB, Radiosurgery of growth hormone-producing pituitary adenomas: Factors associated with biochemical remission: J Neurosurg, 2007; 106(5); 833-38

15. Morikawa T, Thoracoscopic surgery for lung cancer: Ann Thorac Cardiovasc Surg, 2006; 12(6); 383-87

16. Kim B, Kim YS, Kim BM, Effect of soil metal contamination on glyphosate mineralization: Role of zinc in the mineralization rates of two copper-spiked mineral soils: Environ Toxicol Chem, 2011; 30(3); 596-601

17. Vogelzang NJ, Radium-223 dichloride for the treatment of castration-resistant prostate cancer with symptomatic bone metastases: Expert Rev Clin Pharmacol, 2017; 10(8); 809-19

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