Distinct age-dependent phenotypes of abnormal liver function tests derived from national Emergency Department data

1. Study design and data sources

This nationwide retrospective cohort study utilized data from the National Emergency Department Information System (NEDIS), a comprehensive registry capturing ED visits across South Korea. ED visits occurring between January 1, 2019, and December 31, 2023, were analyzed. Patients presenting with abnormal LFTs were identified using the International Classification of Diseases, 10th Revision (ICD-10) code R94.5 (abnormal results of liver function studies). Because NEDIS does not include quantitative laboratory values, this code was used to identify ED visits in which liver function abnormalities represented the primary or a clinically significant presenting concern requiring emergency evaluation, regardless of underlying etiology. Patients were categorized into pediatric (0–18 years) and adult (19–64 years).

2. Clinical variables and outcomes

Clinical variables extracted from NEDIS included patient demographics (age and sex), presenting symptoms at ED arrival, triage acuity, concurrent diagnoses, and disposition outcomes. Triage acuity was assessed using the Korean Triage and Acuity Scale (KTAS), a standardized 5-level triage system used nationwide, and was categorized as high acuity (KTAS levels 1–2), moderate acuity (KTAS level 3), and low acuity (KTAS levels 4–5). Disposition outcomes were classified as discharge from the ED, hospital admission to a general ward, admission to an intensive care unit, or transfer to another facility. Presenting symptoms were identified from structured symptom fields recorded at ED presentation and included fever, gastrointestinal symptoms (nausea, vomiting, or diarrhea), abdominal pain, respiratory symptoms, and other systemic complaints. Systemic symptoms included dizziness, myalgia, chest pain, and generalized weakness. Concurrent diagnoses were identified using ICD-10 codes assigned during the ED visit and were grouped according to major ICD-10 diagnostic chapters to characterize the clinical context accompanying abnormal LFT-related visits.

3. Definition of COVID-19 social distancing periods

To evaluate temporal changes in ED utilization, the study period was divided into 3 phases according to national COVID-19 social distancing policies implemented in South Korea. The predistancing period was defined as January 1, 2019, to March 21, 2020, representing baseline patterns before the introduction of nationwide social distancing measures. The during-distancing period spanned from March 22, 2020, to April 17, 2022, corresponding to sustained government-mandated social distancing and public health interventions. The postdistancing period was defined as April 18, 2022, to December 31, 2023, following the formal lifting of social distancing policies. These period definitions were applied uniformly across all analyses to facilitate comparisons of ED visit patterns between pediatric and adult patients.

4. Infectious pathogen surveillance data

To examine temporal associations between ED visits for abnormal LFTs and circulating infectious pathogens, national infectious disease surveillance data provided by the Korea Disease Control and Prevention Agency (KDCA) were used. ED visit data from NEDIS and pathogen surveillance data from KDCA were analyzed independently at the population level and were not linked at the individual patient level. This surveillance system compiles weekly aggregated reports from designated sentinel institutions across South Korea and monitors community-level circulation of respiratory and enteric pathogens. Respiratory pathogens included rhinovirus, adenovirus, parainfluenza virus, human bocavirus, human metapneumovirus, respiratory syncytial virus, influenza virus, and human coronavirus. Enteric pathogens comprised enteric viruses (astrovirus, sapovirus, norovirus, and rotavirus) and enteric bacteria, including enteropathogenic Escherichia coli (EPEC) and enterotoxigenic Escherichia coli (ETEC).

To analyze population-level temporal relationships between the 2 independent datasets, we performed temporal alignment using contemporaneous weekly data from both NEDIS and KDCA. This approach enabled assessment of temporal correlations between ED visit trends and community-level pathogen circulation patterns, without establishing individual-level linkage. Detailed characteristics of the KDCA surveillance system, including annual sentinel institution numbers, and pathogen case counts, are provided in Supplementary Table 1.

5. Statistical analysis

Descriptive statistics were used to summarize patient characteristics, presenting symptoms, concurrent diagnoses, and disposition outcomes. Categorical variables were reported as frequencies and percentages and were compared between pediatric and adult patients using chi-square tests, as appropriate. Temporal changes in ED visit volumes for abnormal LFTs across COVID-19 periods were evaluated using negative binomial generalized additive models with cyclic splines to account for seasonal patterns and overdispersion in count data. Rate ratios with 95% confidence intervals (CIs) were calculated to compare visit volumes between the predistancing, during-distancing, and postdistancing periods. Analyses were performed separately for pediatric and adult patients. For pairwise comparisons between COVID-19 periods, P values were adjusted using the Bonferroni correction for multiple testing.

Associations between ED visit trends and infectious pathogens were assessed by comparing weekly ED visit counts with weekly pathogen detection counts. Correlation analyses were conducted using Spearman rank correlation coefficients to evaluate population-level associations, and were performed separately for pediatric and adult patients. All statistical analyses were conducted using R ver. 4.4.3 (R Foundation for Statistical Computing, Austria). A 2-sided P value<0.05 was considered statistically significant.

6. Ethical considerations

This study was approved by the institutional review board of Seoul National University Hospital (E-2507-044-1656). The requirement for informed consent was waived due to the retrospective nature of the study and use of deidentified data.

1. Clinical characteristics of patients presenting with abnormal LFTs

Between January 2019 and December 2023, a total of 26,874 ED visits for abnormal LFTs were identified nationwide. Of these, 3,152 visits (11.7%) occurred in pediatric patients aged 0–18 years, while 23,722 visits (88.3%) involved adult patients aged 19–64 years (Fig. 1). Pediatric ED visits remained relatively stable across all age subgroups, while adult visits demonstrated a progressive increase with advancing age, with the most pronounced rise observed in older adult age groups. Pediatric patients demonstrated a male predominance (61.1%), whereas adult patients showed a more balanced sex distribution (54.6%) (P<0.001) (Table 1). Pediatric patients also more frequently presented with high-acuity conditions, with 21.1% classified as KTAS 1–2, compared with 6.4% among adults. Overall admission rates were higher in pediatric patients (72.4%) than in adults (53.3%). Despite this higher initial acuity and admission rate, pediatric patients required intensive care less frequently than adults (1.8% vs. 5.2%). Adults were more likely to be discharged directly from the ED (44.9% vs. 26.7%).

Fig. 1.

Age distribution of Emergency Department visits for abnormal liver function tests, 2019–2023. Bar graph showing the number of Emergency Department (ED) visits by age. The green bars represent pediatric patients (0–18 years), while the orange bars represent adult patients (19–64 years).

Table 1.

Clinical outcomes of patients with abnormal liver function tests presenting to the Emergency Department

2. Presenting symptoms and distribution of concurrent diagnoses in patients with abnormal LFTs

Presenting symptoms at ED presentation differed substantially between pediatric and adult patients (Table 2). Fever was the predominant symptom among pediatric patients, observed in 47.3% of cases and occurring more than 3 times as frequently as in adults (13.9%). Respiratory symptoms were also more common in pediatric patients (6.4% vs. 4.0%). In contrast, adult patients more frequently presented with abdominal pain (26.4% vs. 14.2%) and systemic symptoms, including dizziness, myalgia, chest pain, and asthenia. Gastrointestinal symptoms such as nausea, vomiting, and diarrhea were observed at comparable frequencies in pediatric and adult patients. The distribution of concurrent diagnoses by ICD-10 diagnostic chapters showed marked differences between the 2 groups (Fig. 2). Adult patients demonstrated higher proportions of endocrine/metabolic disorders (16.4%), circulatory diseases (12.4%), and genitourinary disorders (11.8%) compared to pediatric patients, while pediatric patients showed higher rates of infectious disease diagnoses (39.8% vs. 22.4%).

Table 2.

Presenting symptoms of patients with abnormal liver function tests presenting to the Emergency Department

Fig. 2.

Concurrent diagnoses among pediatric and adult patients visiting the Emergency Department for abnormal liver function tests. Horizontal bar chart comparing the proportion of International Classification of Diseases, Tenth Revision, diagnostic categories between pediatric (0–18 years, shown in green) and adult (19–64 years, shown in orange) patients.

Specific disease patterns differed markedly between groups (Supplementary Table 2). Pediatric presentations featured predominantly infectious etiologies including gastroenteritis (15.8%), unspecified viral infections (6.9%), acute bronchitis (4.5%), sepsis (4.3%), and acute viral hepatitis (4.2%). Respiratory viral syndromes including bronchiolitis (3.4%), influenza (2.3%), and viral pneumonia (1.5%) were common, alongside infectious mononucleosis (2.4%) and cytomegaloviral disease (1.7%). Hematologic conditions were prominent, with agranulocytosis occurring in 10.7% and lymphoid leukemia in 6.4% of cases. In contrast, adult patients demonstrated infectious gastroenteritis as the most frequent concurrent diagnosis (20.9%), followed by gastritis (18.3%) and gastroesophageal reflux disease (9.2%). Conditions associated with metabolic syndrome and MASLD were common, including disorders of lipoprotein metabolism (7.9%), hypertension (7.8%), and type 2 diabetes mellitus (6.0%). Liver-specific conditions included alcoholic liver disease (5.1%), other inflammatory liver diseases (4.5%), and acute pancreatitis (3.7%), with viral hepatitis occurring in 3.4% of cases. Overall, pediatric patients exhibited fever-predominant acute respiratory viral infection profiles, while adult patients showed infectious gastroenteritis, upper gastrointestinal disorders, and clustering of cardiometabolic risk factors consistent with metabolic syndrome.

3. Changes in ED visit volume during the COVID-19 period

Given that COVID-19 social distancing measures substantially altered infectious disease epidemiology, ED visit volumes for abnormal LFTs changed differently between pediatric and adult patients across the COVID-19 pandemic periods (Table 3). Among pediatric patients, visit volumes showed nonsignificant declines during the social distancing period and in the postdistancing period compared with the predistancing period. In contrast, adult patients demonstrated a distinct pattern. While visit volumes showed no significant change during the distancing period compared with the predistancing period, visits significantly increased in the postdistancing period compared with the during-distancing period (rate ratio [during/post], 0.82, 95% CI 0.71–0.95; P=0.004). These findings indicate divergent age-dependent changes in ED utilization for abnormal LFTs during and after the COVID-19 pandemic.

Table 3.

Pairwise comparisons of ED visit rates between intervention periods

4. Temporal trends and pathogen associations of abnormal LFT-related visits

To further explore potential factors underlying the divergent changes in ED visit volumes, we examined population-level temporal patterns of visits for abnormal LFTs in relation to infectious pathogen surveillance data (Fig. 3A). In pediatric patients, visit trends showed close temporal alignment with respiratory viral activity, particularly rhinovirus and adenovirus, which exhibited pronounced seasonal fluctuations during the prepandemic period and altered patterns thereafter. Other respiratory viruses, including parainfluenza virus and human bocavirus, demonstrated episodic increases corresponding to pediatric visit peaks. In contrast, adult patients showed temporal patterns that more closely paralleled enteric pathogens. Increases in visits were temporally associated with enteric viruses such as astrovirus and sapovirus, as well as enteric bacterial pathogens including EPEC and ETEC, particularly during the postdistancing period. These population-level temporal patterns were subsequently quantified through correlation analyses (NEDIS-KDCA correlation).

Fig. 3.

Temporal trends and inter-pathogen correlations during the COVID-19 pandemic. (A) Weekly number of Emergency Department (ED) visits by pediatric versus adult population (top 2 panels) and national pathogen detection trends (lower panels) across 3 periods: Predistancing (January 1, 2019 to March 21, 2020), Duringdistancing (March 22, 2020 to April 17, 2022), and postdistancing (April 18, 2022 to December 31, 2023). (B) Spearman correlation matrices of ED visits and pathogen detections in pediatric (upper) and adult (lower) populations. Circle size represents correlation strength (r); color indicates direction (red: positive; blue: negative). ADV, adenovirus; AstV, astrovirus; COVID-19, coronavirus disease 2019; EPEC, enteropathogenic Escherichia coli; ETEC, enterotoxigenic Escherichia coli; EV, enterovirus; Flu, influenza virus; HBoV, human bocavirus; HCoV, human coronavirus; hMPV, human metapneumovirus; NoV, norovirus; PIV, parainfluenza virus; RHV, rhinovirus; RSV, respiratory syncytial virus; RV, rotavirus; SaV, sapovirus

Population-level correlation analyses highlighted age-specific pathogen associations (Fig. 3B, NEDIS-KDCA correlation). Pediatric visits were positively correlated with respiratory viruses, most notably rhinovirus (r=0.30, P<0.001), adenovirus (r=0.28, P<0.001), and parainfluenza virus (r=0.25, P<0.001), whereas correlations with enteric pathogens were weak or nonsignificant. Conversely, adult visits demonstrated stronger positive correlations with enteric viruses, including astrovirus (r=0.35, P<0.001) and sapovirus (r=0.32, P<0.001), as well as enteric bacteria such as EPEC (r=0.38, P<0.001) and ETEC (r=0.36, P<0.001). These temporal correlation patterns at the population level indicate age-specific pathogen profiles, characterized by predominant alignment with respiratory viruses in pediatric patients and with enteric pathogens in adult patients.