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Pediatric Liver Biopsies Over a Decade: Patterns of Disease and Biochemical AssociationsAssistant professor in
AmirhosseinHosseiniM.D)
1,2Emailah_hosseini@sbmu.ac.irA
nedaebnabbasi1,2maryam.abdolmaleki1✉,2Emailmaryam.abdolmaleki97@gmail.com
NeginGholizadeh1✉EmailNegin.Gholizadeh79@gmail.comEmaili@gmail.com
MaryamKazemiaghdam1✉,2EmailM_Kazemi_aghdam@yahoo.com
Assistant professor in
KatayounKhatamiM.D)
1,2NaghiDara
M.D)
1,2,5AliakbarSayyari
M.D)
1,2,5FaridImanzadeh
M.D)
1,2,5NegarImanzadeh1,2,6
MahmoudHajipour1,2
PediatricGastroenterology1✉,2,7Emailgzing@gmail.com
NeginGholizadeh
(MSc)
3MaryamKazemi4
Assistant professor in
ayehyaraghi11
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Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s HealthShahid Beheshti University of Medical SciencesTehranIran2
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school of medicineShahid beheshti university of medical sciencesTehraniran3
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MSc studentsDept of epidemiology school of public health and safety shahid beheshtiUniversity of medical sciencesTehraniran4
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Pediatric pathology, Hepatology and Nutrition Research Center, Research Institute for Children’s HealthShahid Beheshti University of Medical SciencesTehranIran5
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Pediatric Gastroenterology Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s HealthShahid Beheshti University of Medical SciencesTehranIran6
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School of PharmacyShahid Beheshti University of Medical SciencesTehranIran7
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Hepatology and Nutrition Research Center, Research Institute for Children’s HealthShahid Beheshti University of Medical SciencesTehranIranAmirhossein Hosseini1, neda ebn abbasi2*, maryam.abdolmaleki3, NeginGholizadeh4, Maryam Kazemi aghdam5, Katayoun Khatami6, Naghi Dara7, Aliakbar Sayyari8, Farid Imanzadeh9, Negar Imanzadeh10,, Mahmoud Hajipour*
1- Amirhossein Hosseini (M.D)
Assistant professor in Pediatric Gastroenterology
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Email: ah_hosseini@sbmu.ac.ir
ORCID ID: 0000-0001-8103-8833
2-neda ebn abbasi(MD) )* (Co Corresponding author)
school of medicine, Shahid beheshti university of medical sciences, Tehran, iran
Email:gzing@gmail.com
3-maryam.abdolmaleki (MD)
school of medicine, Shahid beheshti university of medical sciences, Tehran, iran
Email : maryam.abdolmaleki97@gmail.com
Orcid id : 0009-0001-8460-8974
4- Negin Gholizadeh(MSc)
MSc studentsDept of epidemiology school of public health and safety shahid beheshti University of medical sciencesTehran,iran
Email:Negin.Gholizadeh79@gmail.com
ORCID ID: 0000-0003-0897-5972
5-Maryam Kazemi aghdam
Assistant professor of pathology
Pediatric pathology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Email:M_Kazemi_aghdam@yahoo.com
ORCID ID:00989122761670
6-Katayoun Khatami (M.D)
Assistant professor in Pediatric Gastroenterology
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Email: kathy.khatami@gmail.com
ORCID ID: 0000-0003-3353-8790
7-Naghi Dara (M.D)
Associated professor in Pediatric Gastroenterology
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Email: drdara49@yahoo.com
ORCID ID:
0000-0002-1881-8893
8-Aliakbar Sayyari (M.D)
Professor in Pediatric Gastroenterology
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Email: drsayyari@hotmail.com
ORCID ID: 0000-0001-8720-3932
9-Farid Imanzadeh (M.D)
Professor in Pediatric Gastroenterology
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Email: drimanzadeh@sbmu.ac.ir
10-Negar Imanzadeh
School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
ORCID ID:0000-0003-0382-9431
11-ayeh yaraghi
Assistant professor in Pediatric Gastroenterology
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Email:avayaraghi@gmail.com
12-Mahmoud Hajipour* Corresponding author)
Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Email: m.hajipour.13@gmail.com
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Abstract
Background
Liver biopsy remains the definitive diagnostic tool for pediatric liver disease, particularly when non-invasive assessments are inconclusive. This study aimed to characterize histopathological findings and associated laboratory abnormalities in a large pediatric cohort undergoing liver biopsy.
Methods
A retrospective cross-sectional study was conducted on 1,158 patients under 18 years of age who underwent liver biopsy at Mofid Children’s Hospital between 2011 and 2021. Data on demographics, biopsy type, histopathological findings, and laboratory parameters were extracted from medical records. Statistical analyses included descriptive statistics and group comparisons using chi-square, t-tests, and non-parametric tests.
Results
Ultrasound-guided needle biopsy was the most frequently performed technique (470, 40.6%). Predominant histopathological features included inflammatory infiltration (797, 68.8%), fibrosis (694, 59.9%), and feathery degeneration (607, 52.4%) (Fig. 1: distribution of common pathological findings). Non-specific changes (252, 21.8%), metabolic liver disease (170, 14.7%), and Wilson’s disease (108, 9.3%) were the most common diagnoses (Fig. 3: common CLINICAL CONDITIONS). Elevated aminotransferases were frequent (mean AST 230.43 U/L, mean ALT 166.00 U/L). Cirrhosis was significantly more prevalent in female patients (p = 0.002). Statistically significant associations were observed between biopsy type and specific histopathological findings (p < 0.001, Tables 2 & 3).
Conclusion
Despite advances in non-invasive diagnostics, liver biopsy remains crucial in pediatric hepatology. The findings underscore its diagnostic value, especially in cases with elevated liver enzymes or nonspecific clinical presentations, while highlighting the need for complementary non-invasive strategies.
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Introduction
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Pediatric liver diseases can significantly impact essential physiological functions such as metabolism, immune regulation, and energy storage(1). Although liver disease is less common in children than in adults, its consequences are more profound. Chronic hepatobiliary conditions in pediatric patients greatly affect their overall health and quality of life, influence life expectancy, place emotional and financial strain on families, and contribute substantially to healthcare costs(2). These conditions may arise from a wide range of causes, including genetic mutations, metabolic disorders, autoimmune conditions, infections, and structural abnormalities(3, 4, 5). In many cases, children present with nonspecific symptoms such as fatigue, failure to thrive, or gastrointestinal complaints, which can make early diagnosis challenging(6, 7, 8). Occasionally, biochemical abnormalities are the only clue, even in the absence of overt clinical signs(9).Among the available diagnostic tools, liver biopsy continues to serve as the gold standard for determining the exact nature and severity of liver disease(10). It offers direct histopathological assessment that can support or refine clinical and laboratory-based diagnoses(11). For example, copper accumulation observed in liver tissue may point to Wilson’s disease, while the presence of portal inflammation and interface hepatitis may suggest autoimmune hepatitis(12, 13). Although imaging and laboratory tests such as ALT, AST, ALP, and serum bilirubin levels play a vital role in evaluating liver function, they often lack the specificity needed for definitive diagnosis(14, 15).
Liver biopsy techniques include percutaneous (ultrasound-guided), laparoscopic, and transjugular approaches, each selected based on patient age, coagulation status, and the need for extensive tissue sampling(16). Despite its diagnostic value, liver biopsy is associated with several limitations, including procedural risks, the need for anesthesia in young children, and potential sampling errors(17, 18).
Given these challenges and the crucial role of accurate diagnosis in guiding treatment and prognosis, this study aims to investigate the histopathological features and corresponding laboratory findings in pediatric liver biopsies performed at Mofid children hospital between 2011 and 2021. By analyzing the patterns of liver pathology alongside clinical and biochemical data, this research seeks to improve understanding of pediatric liver diseases, support timely diagnosis, and contribute to more effective, evidence-based clinical decision-making and management strategies.
Methods
Study Design
This retrospective cross-sectional study investigated histopathological findings and laboratory outcomes in pediatric patients undergoing liver biopsy at Mofid Children’s Hospital. Data included laboratory test results for AST, ALT, ALP, albumin, INR, total and direct bilirubin, uric acid, and phosphate.
Study Population
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All patients under 18 years who underwent liver biopsy at Mofid Children’s Hospital between 2011 and 2021 were included.Inclusion and Exclusion Criteria
Inclusion: Patients under 18 years who underwent liver biopsy.
Exclusion: Patients with incomplete biopsy reports or missing laboratory data, or those referred for non-liver-related studies.
Data Collection and Variables
Demographics, biopsy type, histopathology results, and laboratory findings were extracted from medical records. Histopathological diagnoses included cirrhosis, hepatitis, and other liver diseases. Laboratory variables included AST, ALT, ALP, total and direct bilirubin, INR, albumin, uric acid, and phosphate.
Statistical Analysis
Data were entered into SPSS version 23. Descriptive statistics included means, SDs, medians, and interquartile ranges. Comparisons used t-tests, chi-square tests, and Mann-Whitney U tests. Crosstabulations and correlation analyses were performed. Logistic regression explored predictors of clinical outcomes.
Ethics
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The study was approved by the relevant ethics committee. Patient data were handled confidentially, and informed consent was obtained.Results
A total of 1,158 pediatric patients were included: 624 males (53.9%) and 534 females (46.1%), with a mean age of 45.55 months (SD = 57.96). Patient demographics and biopsy types are presented in Table 1
Variable | Frequency (n) | Percentage (%) |
|---|---|---|
Gender | ||
Male | 150 | 57.3 |
Female | 112 | 42.7 |
Type of Ingested Substance | ||
Acid | 71 | 27.1 |
Bleach | 39 | 14.9 |
Alkali | 150 | 57.3 |
Form of Ingested Substance | ||
Liquid | 252 | 96.2 |
Other | 8 | 3.1 |
Volume of Ingestion | ||
Less than 5 cc | 20 | 7.6 |
5 to 10 cc | 223 | 85.1 |
More than 10 cc | 14 | 5.3 |
Biopsy Types
The most common biopsy technique was ultrasound-guided needle biopsy (470, 40.6%). Other methods included liver biopsy/cyst/tissue (287, 24.8%), liver wedge biopsy (220, 19%), liver mass biopsy (147, 12.7%), and open biopsy (25, 2.2%) (Table 1).
category | Finding | Percentage | Count |
|---|---|---|---|
Sex | male | 53.9 | 624 |
female | 46.1 | 534 | |
Biopsy type | liver needle biopsy | 40.6 | 470 |
liver mass | 12.7 | 147 | |
liver biopsy/cyst/tissue | 24.8 | 287 | |
necropsy/autopsy | 0.8 | 9 | |
open biopsy | 2.2 | 25 | |
liver wedge biopsy | 19 | 220 | |
common Pathological Findings | giant cell transformation | 27 | 313 |
fibrous expansion of portal space | 39.9 | 462 | |
portal fibrosis | 44 | 510 | |
bridging fibrosis | 32 | 370 | |
fibrosis | 59.9 | 694 | |
feathery degeneration | 52.4 | 607 | |
inflammatory cell | 68.8 | 797 | |
macro vesicular steatosis | 15.3 | 177 | |
micro vesicular steatosis | 32.6 | 378 | |
ductular proliferation | 25.1 | 291 | |
glycogenated nuclei | 20 | 232 | |
interface hepatitis | 15.9 | 184 | |
cholestasis | 34.7 | 402 | |
eosinophil in portal space | 25.6 | 297 | |
cirrhosis | 16.1 | 187 | |
bile plug | 14.5 | 168 | |
extramedullary hematoposis | 15.9 | 184 | |
acinar transformation | 26 | 301 | |
pseudo acinar transformation | 13.6 | 158 | |
hepatocyte loss | 33.2 | 384 | |
Common Clinical Conditions | Wilson disease | 9.3 | 108 |
metabolic disease | 14.7 | 170 | |
Autoimmune hepatitis | 8 | 93 | |
Biliary atresia | 10.9 | 126 | |
Non specific change | 21.8 | 252 | |
GSD | 6.6 | 77 | |
hepatoblastoma | 7.3 | 84 | |
Common Symptoms | Elevated liver azymes | 26.3 | 304 |
organomegaly | 19.9 | 231 | |
Icter + Jaundice | 9.8 | 114 | |
Hepatic mass | 5.7 | 66 | |
Cholestasis | 4.8 | 56 |
Histopathological Findings
The predominant findings were inflammatory cell infiltration (797, 68.8%), fibrosis (694, 59.9%), and feathery degeneration (607, 52.4%). Portal fibrosis was observed in 510 patients (44%) and fibrous expansion in 462 (39.9%) (Fig. 1(
Fig. 1
distribution of common pathological findings
Diagnosed Liver Diseases
Non-specific changes (252, 21.8%), metabolic disorders (170, 14.7%), and Wilson’s disease (108, 9.3%) were most frequent (Fig. 3).
Fig. 3
common CLINICAL CONDITIONS
Clinical Findings
Abnormal liver enzymes were present in 304 patients (26.3%), organomegaly in 231 (19.9%), and jaundice/icterus in 114 (9.8%) (Fig. 2).
Fig. 2
common signs and symptoms
Laboratory Evaluations
Mean AST and ALT levels were 230.43 U/L (SD = 340.74) and 166.00 U/L (SD = 276.78), with maximums of 3,800 U/L and 4,063 U/L. Mean ALP was 842.39 U/L, total bilirubin 6.27 mg/dL, direct bilirubin 3.59 mg/dL, INR 1.19 (SD = 0.75), and albumin 3.79 g/dL. Uric acid and phosphate were within normal limits.
Biopsy Types by Gender
Needle biopsy was most common in both males (244) and females (226, p = 0.489). Fibrosis distribution was similar (359 males vs. 335 females, p = 0.072), whereas cirrhosis was more prevalent in females (106 vs. 81 males, p = 0.002) (Table 2).
Type | Girls | Boys | P value | |
|---|---|---|---|---|
Biopsy | Liver needle biopsy | 226 | 244 | 0.489 |
Liver mass | 67 | 80 | ||
cyst/tissue | 134 | 153 | ||
Necropsy/autopsy | 2 | 7 | ||
Open biopsy | 1 | 2 | ||
Liver wedge biopsy | 96 | 124 | ||
Pathology | Fibrosis | 335 | 359 | 0.072 |
Cirrhosis | 60 | 81 | 0.002 | |
Edema | 2 | 3 | 0.783 | |
Hepatic necrosis | 28 | 37 | 0.613 | |
Disease | Wilson disease | 45 | 63 | 0.33 |
Metabolic disease | 72 | 98 | 0.29 | |
Storage disease | 10 | 16 | 0.429 |
Category | Subcategory | Frequency (n) | Percentage (%) |
|---|---|---|---|
Upper GI Injury | Yes | 105 | 40.1 |
No | 156 | 59.5 | |
Acute Complications | None | 154 | 58.8 |
Perforation | 3 | 1.1 | |
Pneumothorax | 1 | 0.4 | |
Mediastinitis | 1 | 0.4 | |
Death | 1 | 0.4 | |
Other | 6 | 2.3 | |
Chronic Complications | None | 115 | 43.9 |
Esophageal Stricture | 26 | 9.9 | |
Jejunostomy | 2 | 0.8 | |
Gastritis | 9 | 3.4 | |
Death | 1 | 0.4 | |
Other | 12 | 4.0 |
Lesion and Disease Distribution by Biopsy Type
Cirrhosis, edema, and hepatic necrosis, as well as Wilson’s disease, metabolic disorders, storage diseases, and Niemann-Pick disease distributions, are detailed in Table 3: distribution of injury and disease type by biopsy.
Variable | Category | Acid (n, %) | Bleach (n, %) | Alkali (n, %) |
|---|---|---|---|---|
Form of Substance | Liquid | 64 (90.1%) | 39 (100%) | 149 (99.3%) |
Other | 7 (9.9%) | 0 (0.0%) | 1 (0.7%) | |
Volume Ingested | < 5 cc | 5 (7.0%) | 4 (10.3%) | 11 (7.3%) |
5–10 cc | 62 (87.3%) | 31 (79.5%) | 130 (86.7%) | |
> 10 cc | 2 (2.8%) | 4 (10.3%) | 8 (5.3%) |
Multivariate Analysis
Logistic regression results for predictors of clinical outcomes are summarized in )Table 4(.Significant variables included age, female gender (protective), jaundice (risk factor), and interface hepatitis (strongest risk factor).
Biopsy type | P- Value | |||||||
liver needle biopsy | Liver mass | liver biopsy /cyst/tissue | necropsy/autopsy | Open Biopsy | liver wedge biopsy | |||
Pathology Type | cirrhosis | 62 | 5 | 68 | 1 | 4 | 47 | 0.001 |
edema | 0 | 1 | 2 | 0 | 0 | 2 | 0.001 | |
Hepatic necrosis | 18 | 3 | 35 | 2 | 0 | 7 | 0.001 | |
Disease type | Wilson disease | 88 | 0 | 19 | 0 | 0 | 1 | 0.001 |
Metabolic disease | 16 | 0 | 7 | 0 | 0 | 3 | 0.164 | |
Storage disease | 78 | 1 | 50 | 1 | 2 | 38 | 0.001 | |
Nimann pick disease | 5 | 0 | 1 | 0 | 0 | 0 | 0.42 | |
Crude | Adjusted | |||||||
|---|---|---|---|---|---|---|---|---|
OR | P-value | Cl 95% | OR | P-value | Cl 95% | |||
lower | upper | lower | upper | |||||
Age | 1.015 | < 0.001 | 1.012 | 1.018 | 1.016 | < 0.001 | 1.011 | 1.021 |
Gender(f) | 0.819 | 0.331 | 0.549 | 1.224 | 0.423 | 0.012 | 0.216 | 0.828 |
Icter + Jaundice (1) | 1.549 | 0.141 | 0.865 | 2.776 | 2.158 | 0.018 | 0.822 | 5.060 |
Cholestasis (1) | 0.738 | 0.566 | 0.262 | 2.082 | 1.530 | 0.563 | 0.362 | 6.477 |
Bill Direct | 0.898 | 0.012 | 0.826 | 0.977 | 1.079 | 0.580 | 0.823 | 1.415 |
Bill Total | 0.922 | 0.004 | 0.872 | 0.974 | 0.903 | 0.258 | 0.756 | 1.078 |
Cirrhosis (1) | 0.563 | 0.081 | 0.296 | 1.073 | 0.411 | 0.106 | 0.140 | 1.207 |
Interface Hepatitis (1) | 12.482 | < 0.001 | 8.060 | 19.112 | 7.019 | < 0.001 | 3.358 | 14.671 |
Fibrosis (1) | 2.385 | < 0.001 | 1.5 | 3.792 | 1.327 | 0.482 | 0.603 | 2.919 |
Ballooning degeneration (1) | 1.449 | 0.449 | 0.555 | 3.786 | 4.076 | 0.061 | 0.935 | 17.769 |
Constant | 0.078 | < 0.001 | 0.023 | < 0.001 | ||||
Complication | Acid (n, %) | Bleach (n, %) | Alkali (n, %) |
|---|---|---|---|
Upper GI Injury | |||
Yes | 33 (46.5%) | 23(59%) | 98 (65.3%) |
No | 38 (53.5%) | 16 (41%) | 51 (34%) |
Acute Complications | |||
None | 44 (62%) | 35 (89.7%) | 74 (49.3%) |
Perforation | 0 (0.0%) | 0 (0.0%) | 3 (2.0%) |
Pneumothorax | 0 (0.0%) | 1 (2.6%) | 0 (0.0%) |
Mediastinitis | 0 (0.0%) | 0 (0.0%) | 1 (0.7%) |
Other | 2 (2.8%) | 0 (0.0%) | 4 (2.7%) |
Death (Acute) | 1 (1.4%) | 0 (0.0%) | 0 (0.0%) |
Chronic Complications | |||
None | 35 (49.3%) | 33 (84.6%) | 46 (30.7%) |
Esophageal Stricture | 8 (11.3%) | 2 (5.1%) | 16 (10.7%) |
Jejunostomy | 1 (1.4%) | 0 (0.0%) | 1 (0.7%) |
Death (Chronic) | 1 (1.4%) | 0 (0.0%) | 0 (0.0%) |
Gastritis | 0 (0.0%) | 0 (0.0%) | 9 (6.0%) |
Other | 4 (5.6%) | 1 (2.6%) | 7 (4.7%) |
Outcome Category | Specific Outcome | Male (n, %) | Female (n, %) |
|---|---|---|---|
Upper GI Tract Injury | Present | 88 (58.5%) | 68 (60.7%) |
Absent | 61 (40.7%) | 44 (39.3%) | |
Acute Complications | None | 89 (59.3%) | 65 (58.0%) |
Perforation | 2 (1.3%) | 1 (0.9%) | |
Pneumothorax | 1 (0.7%) | 0 (0.0%) | |
Death | 0 (0.0%) | 1 (0.9%) | |
Mediastinitis | 0 (0.0%) | 1 (0.9%) | |
Other | 2 (1.3%) | 4 (3.6%) | |
Chronic Complications | None | 66 (44.0%) | 49 (43.8%) |
Esophageal stricture | 17 (11.3%) | 9 (8.0%) | |
Jejunostomy | 1 (0.7%) | 1 (0.9%) | |
Gastritis | 3 (2.0%) | 6 (5.4%) | |
Death | 0 (0.0%) | 1 (0.9%) | |
Other | 8 (5.3%) | 4 (3.6%) |
Variable | Upper GI Injury Chi-Square (p-value) | Acute Complications Chi-Square (p-value) | Chronic Complications Chi-Square (p-value) |
|---|---|---|---|
Gender | 4.62 (p = 0.463) | 4.90 (p = 0.427) | 0.073 (p = 0.787) |
Type of Substance | 7.43 (p = 0.024) * | 11.09 (p = 0.049) * | 21.40 (p = 0.018) * |
Form of Substance | 1.68 (p = 0.891) | 11.14 (p = 0.049) * | 10.50 (p = 0.001) * |
Volume Ingested | 17.20 (p < 0.001) * | 33.90 (p < 0.001) * | 45.80 (p < 0.001) * |
Discussion
Our retrospective study, encompassing over a thousand pediatric patients, provides a comprehensive overview of liver biopsy practices, histopathological findings, and associated clinical variables in a large pediatric cohort. The predominance of liver needle biopsy (40.6%) as the preferred method aligns with international trends, as it is minimally invasive and provides sufficient tissue for histological evaluation in most pediatric liver diseases(19, 20).
Histopathological analysis revealed inflammatory cell infiltration (68.8%), fibrosis (59.9%), and feathery degeneration (52.4%) as the most frequent findings, consistent with previous studies emphasizing chronic hepatitis, autoimmune hepatitis, and metabolic liver diseases as major causes of pediatric liver pathology (3, 21). Notably, cirrhosis was significantly more common in female patients (p = 0.002), a finding warranting further investigation, although a few studies have reported different sex-based trends in chronic liver injury progression(22, 23).
Detecting portal fibrosis (in 44% of cases) and fibrous expansion (in 39.9%) shows that liver biopsy is useful for determining the early stage of liver diseases like biliary atresia and Wilson’s disease. These conditions often develop early scarring in the liver that cannot be clearly seen with imaging or blood tests alone(24, 25). In our study, Wilson’s disease, metabolic disorders, and storage diseases were more frequently diagnosed through liver needle biopsy and cyst/tissue biopsies, reinforcing their diagnostic role in systemic or diffuse hepatic pathologies.
One of the most important findings of our study was the investigation of the relationship between biochemical abnormalities and clinical symptoms with histopathological findings. Abnormal liver enzymes were observed in 26.3% of patients with gastrointestinal symptoms, indicating possible underlying liver involvement. Additionally, hepatomegaly was present in 19.9% of patients, and jaundice was seen in 9.8% of cases.
The relatively high levels of liver enzymes, especially AST and ALT, with extreme outliers (AST up to 3,800 U/L, ALT up to 4,063 U/L), indicate that many biopsies were likely performed in the context of acute liver injury. While such elevations are not exclusive to any single condition, they often prompt biopsy to distinguish between acute and chronic hepatic processes or to evaluate for metabolic or autoimmune etiologies(26, 27).
The study by Ovchinsky et al. (2012) confirms that liver biopsy remains a valuable diagnostic tool in the evaluation of pediatric liver diseases. However, with the advancement of non-invasive methods such as imaging and biomarkers, its role is gradually shifting. This is consistent with our findings, which also highlight that although liver biopsy continues to be the diagnostic gold standard, its invasive nature and associated costs underscore the growing need for effective non-invasive alternatives(28).
The study by Sathe et al. (2017) showed that prolonged jaundice, acholic stools, abdominal distension, metabolic diseases, and suspicion of liver masses were the most common reasons for performing liver biopsy(29). Similarly, in the study by Baquero et al. (2015), these were among the most common indications for gastrointestinal liver biopsy. These findings are comparable to the results of our study(30). This also aligns with our study, as a considerable proportion of patients in our study also presented with jaundice and organomegaly.
In another study in pediatric patients with liver diseases, it was determined that new techniques such as elastography and FibroScan, although valuable and less invasive, still cannot replace liver biopsy due to limitations such as variability in results based on age, weight, and equipment used, lack of standardization in measurement protocols, operator dependency, inconsistent findings across studies, and reduced accuracy in certain disease groups—thus, liver biopsy remains the gold standard(31, 32). This is also consistent with our study, in which liver biopsy was considered the gold standard for a definite diagnosis.
Accordingly, our study aligns with many aspects of previous research, particularly regarding the importance of liver biopsy, the most common indications for its performance, and the limitations of non-invasive methods. However, some differences may exist in our study, which could be attributed to varying demographic and environmental factors, as well as differences in diagnostic approaches and sampling techniques. Ultimately, our findings may contribute to a better understanding of the role of liver biopsy and help refine diagnostic strategies for patients with liver disease.
Limitations
Some limitations of this study include its cross-sectional design and reliance on data extracted from patient records, which may have included incomplete information or documentation errors. Furthermore, the lack of direct comparison between biopsy findings and non-invasive diagnostic methods such as FibroScan or MRI represents another limitation. Therefore, future studies with longitudinal designs and direct comparisons between invasive and non-invasive modalities are recommended
Conclusion
This large retrospective study confirms the essential role of liver biopsy in pediatric hepatology. Needle biopsy is minimally invasive and diagnostically effective, with inflammatory infiltration and fibrosis being the most frequent findings. Associations between pathological changes and abnormal liver enzymes emphasize integrating histopathology with clinical and laboratory data to improve diagnostic accuracy and guide management.
Abbreviations
Abbreviations
• AST
Aspartate Aminotransferase
• ALT
Alanine Aminotransferase
• ALP
Alkaline Phosphatase
• INR
International Normalized Ratio
• SD
Standard Deviation
• SPSS
Statistical Package for the Social Sciences
• CI
Confidence Interval
• OR
Odds Ratio
• Cl 95%
95% Confidence Interval
• U/L
Units per Liter
• g/dL
grams per deciliter
• mg/dL
milligrams per deciliter
• GSD
Glycogen Storage Disease
• MRI
Magnetic Resonance Imaging
• ESPGHAN
European Society for Paediatric Gastroenterology, Hepatology and Nutrition
Declarations
Ethics approval and consent to participate
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Approved by Ethics Committee of the School of Medicine, ShahidBeheshtiUniversity of medical sciences number) IR.SBMU.MSP.REC.1401.575) Written informed consent obtained from all participants.Consent for publication
Not applicable.
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Data Availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Competing interests
The authors declare that they have no conflicts of interest related to the design, conduct, or reporting of this study.
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Funding:
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors
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Author Contribution
AH conceived the study; NA collected data; MH analyzed data;NG editor ;all authors contributed to writing and approved the final manuscript.
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Acknowledgement
The authors would like to express their sincere appreciation to the medical and nursing staff of Mofid Children’s Hospital for their invaluable assistance in patient care and data collection. We are also grateful to the patients and their families for their cooperation, which made this study possible
Electronic Supplementary Material
Below is the link to the electronic supplementary material
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