Pediatric Liver Biopsies Over a Decade: Patterns of Disease and Biochemical Associations

Pediatric Liver Biopsies Over a Decade: Patterns of Disease and Biochemical Associations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pediatric Liver Biopsies Over a Decade: Patterns of Disease and Biochemical Associations Amirhossein Hosseini, neda ebn abbasi, maryam. abdolmaleki, Negin Gholizadeh, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7617977/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version 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. Figures Figure 1 Figure 2 Figure 3 Introduction 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 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 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 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 ). Table 1 . Summary of All Demographic Features and Biopsy types and most prevalent Pathological and Disease Findings 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%) ( Figure 1 ( Diagnosed Liver Diseases Non-specific changes (252, 21.8%), metabolic disorders (170, 14.7%), and Wilson’s disease (108, 9.3%) were most frequent (Figure 3). 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 ). Table 2. distribution of biopsy, pathology and disease type by gender P value Boys Girls Type 0.489 244 226 Liver needle biopsy Biopsy 80 67 Liver mass 153 134 cyst/tissue 7 2 Necropsy/autopsy 2 1 Open biopsy 124 96 Liver wedge biopsy 0.072 359 335 Fibrosis Pathology 0.002 81 60 Cirrhosis 0.783 3 2 Edema 0.613 37 28 Hepatic necrosis 0.33 63 45 Wilson disease Disease 0.29 98 72 Metabolic disease 0.429 16 10 Storage disease 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 . 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). Table 3. distribution of injury and disease type by biopsy 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 Table 4. logistic regression model summary 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 _ _ 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 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 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. Availability of data and materials 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. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors Authors’ contributions: AH conceived the study; NA collected data; MH &NG analyzed data; all authors contributed to writing and approved the final manuscript. Acknowledgments 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 References Kalra A, Yetiskul E, Wehrle CJ, Tuma F. Physiology, Liver. StatPearls. Treasure Island (FL)2025. Arya G, Balistreri WF. Pediatric liver disease in the United States: epidemiology and impact. J Gastroenterol Hepatol. 2002;17(5):521-5. 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18:52:46","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":139393,"visible":true,"origin":"","legend":"","description":"","filename":"fdb871e553b5454893b3d80d331dbbcd1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7617977/v1/5f02ae650595228959665bcb.xml"},{"id":92744738,"identity":"7184fbc4-8e58-4865-a476-7dc4f413f15c","added_by":"auto","created_at":"2025-10-03 18:52:46","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":155574,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7617977/v1/07938d4c08a79c5f86a5afa3.html"},{"id":92744720,"identity":"80bb8e23-de83-4082-9101-dc4786bb4cfa","added_by":"auto","created_at":"2025-10-03 18:52:46","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":124721,"visible":true,"origin":"","legend":"\u003cp\u003edistribution of common pathological findings\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7617977/v1/3a311ed56d567cf4a0b3f1d1.jpg"},{"id":92745653,"identity":"2ca2024c-0e3a-4c2c-9d3d-38c6780a97c3","added_by":"auto","created_at":"2025-10-03 19:00:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":35227,"visible":true,"origin":"","legend":"\u003cp\u003ecommon signs and symptoms\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7617977/v1/710037d1cd2538cb39e639e5.jpg"},{"id":92744721,"identity":"2b3fb88f-7c6d-48f6-9217-9e6bd02e2e97","added_by":"auto","created_at":"2025-10-03 18:52:46","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":51864,"visible":true,"origin":"","legend":"\u003cp\u003ecommon CLINICAL CONDITIONS\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7617977/v1/6bb500cfc141963cf4137363.jpg"},{"id":94475221,"identity":"c29b14e7-2819-4b5d-a70f-b6e897bfec8d","added_by":"auto","created_at":"2025-10-27 15:51:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1418495,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7617977/v1/df58b87e-ebfb-4b4a-8c2a-ae3228db9f22.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pediatric Liver Biopsies Over a Decade: Patterns of Disease and Biochemical Associations","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePediatric liver diseases can significantly impact essential physiological functions such as metabolism, immune regulation, and energy storage(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). 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(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). These conditions may arise from a wide range of causes, including genetic mutations, metabolic disorders, autoimmune conditions, infections, and structural abnormalities(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In many cases, children present with nonspecific symptoms such as fatigue, failure to thrive, or gastrointestinal complaints, which can make early diagnosis challenging(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Occasionally, biochemical abnormalities are the only clue, even in the absence of overt clinical signs(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAmong the available diagnostic tools, liver biopsy continues to serve as the gold standard for determining the exact nature and severity of liver disease(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). It offers direct histopathological assessment that can support or refine clinical and laboratory-based diagnoses(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). For example, copper accumulation observed in liver tissue may point to Wilson\u0026rsquo;s disease, while the presence of portal inflammation and interface hepatitis may suggest autoimmune hepatitis(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). 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(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eLiver 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(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). 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(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eGiven 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.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design\u003c/h2\u003e\u003cp\u003eThis retrospective cross-sectional study investigated histopathological findings and laboratory outcomes in pediatric patients undergoing liver biopsy at Mofid Children\u0026rsquo;s Hospital. Data included laboratory test results for AST, ALT, ALP, albumin, INR, total and direct bilirubin, uric acid, and phosphate.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy Population\u003c/h3\u003e\n\u003cp\u003eAll patients under 18 years who underwent liver biopsy at Mofid Children\u0026rsquo;s Hospital between 2011 and 2021 were included.\u003c/p\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eInclusion\u003c/b\u003e: Patients under 18 years who underwent liver biopsy.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eExclusion\u003c/b\u003e: Patients with incomplete biopsy reports or missing laboratory data, or those referred for non-liver-related studies.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\n\u003ch3\u003eData Collection and Variables\u003c/h3\u003e\n\u003cp\u003eDemographics, 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.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eData 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.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eEthics\u003c/h2\u003e\u003cp\u003e The study was approved by the relevant ethics committee. Patient data were handled confidentially, and informed consent was obtained.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA 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 \u003cstrong\u003eTable 1\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiopsy Types\u003c/strong\u003e\u003cbr\u003eThe 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%) (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable\u0026nbsp;\u003c/em\u003e\u003cem\u003e1\u003c/em\u003e\u003cem\u003e. Summary of All Demographic Features and Biopsy types and most prevalent Pathological and Disease Findings\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"620\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFinding\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCount\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e53.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e624\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e46.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e534\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBiopsy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eliver needle biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e40.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e470\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eliver mass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e12.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e147\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eliver biopsy/cyst/tissue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e24.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e287\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003enecropsy/autopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eopen biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eliver wedge biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecommon Pathological\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFindings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003egiant cell transformation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003efibrous expansion of portal space\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e39.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eportal fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e510\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003ebridging fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e370\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003efibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e59.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e694\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003efeathery degeneration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e52.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e607\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003einflammatory cell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e68.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e797\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003emacro vesicular steatosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e15.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e177\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003emicro vesicular steatosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e32.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e378\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eductular proliferation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e25.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e291\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eglycogenated nuclei\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e232\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003einterface hepatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e15.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003echolestasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e34.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eeosinophil in portal space\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e297\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003ecirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e16.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e187\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003ebile plug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e168\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eextramedullary hematoposis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e15.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eacinar transformation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e301\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003epseudo acinar transformation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003ehepatocyte loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e33.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e384\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCommon Clinical Conditions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eWilson disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003emetabolic disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e14.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eAutoimmune hepatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eBiliary atresia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eNon specific change\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e21.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eGSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e6.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003ehepatoblastoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCommon\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eSymptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eElevated liver azymes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e26.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eorganomegaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e19.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e231\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eIcter+Jaundice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eHepatic mass\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 202px;\"\u003e\n \u003cp\u003eCholestasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathological Findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 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%) (\u003cstrong\u003eFigure 1\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e(\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e\u003cstrong\u003eDiagnosed Liver Diseases\u003c/strong\u003e\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003eNon-specific changes (252, 21.8%), metabolic disorders (170, 14.7%), and Wilson\u0026rsquo;s disease (108, 9.3%) were most frequent (Figure 3).\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory Evaluations\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;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.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiopsy Types by Gender\u003c/strong\u003e\u003cbr\u003eNeedle 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) (\u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTable\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e2. distribution of biopsy, pathology and disease type by gender\u003c/em\u003e\u003c/p\u003e\n\u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eBoys\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eGirls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.489\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eLiver needle biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eBiopsy\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eLiver mass\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ecyst/tissue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eNecropsy/autopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eOpen biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eLiver wedge biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eFibrosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePathology\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eCirrhosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.783\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eEdema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eHepatic necrosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eWilson disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eDisease\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eMetabolic disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp dir=\"LTR\"\u003e0.429\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 111px;\"\u003e\n \u003cp dir=\"LTR\"\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp dir=\"LTR\"\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eStorage disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eLesion and Disease Distribution by Biopsy Type\u003c/strong\u003e\u003cbr\u003eCirrhosis, edema, and hepatic necrosis, as well as Wilson\u0026rsquo;s disease, metabolic disorders, storage diseases, and Niemann-Pick disease distributions, are detailed in \u003cstrong\u003eTable 3: distribution of injury and disease type by biopsy\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultivariate Analysis\u003c/strong\u003e\u003cbr\u003e Logistic regression results for predictors of clinical outcomes are summarized in )\u003cstrong\u003eTable 4\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e(\u003c/span\u003e\u003c/strong\u003e.Significant variables included age, female gender (protective), jaundice (risk factor), and interface hepatitis (strongest risk factor).\u003c/p\u003e\n\u003cp\u003eTable 3. distribution of injury and disease type by biopsy\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"676\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 164px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 460px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBiopsy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP- Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eliver needle biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver mass\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eliver biopsy /cyst/tissue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003enecropsy/autopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOpen Biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eliver wedge biopsy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePathology\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecirrhosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eedema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHepatic necrosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eDisease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003etype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWilson disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetabolic disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStorage disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNimann pick disease\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 51px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 52px;\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 4. logistic regression model summary\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"672\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 282px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCrude\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCl 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCl 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003elower\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eupper\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003elower\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eupper\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e1.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e1.021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eGender(f)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.549\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.224\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.828\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eIcter+Jaundice (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.549\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.865\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e2.776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e2.158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e5.060\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCholestasis (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.566\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e2.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.530\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.563\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.362\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e6.477\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eBill Direct\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.898\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.826\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.580\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.823\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e1.415\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eBill Total\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.922\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.756\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e1.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eCirrhosis (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.563\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.411\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e1.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eInterface Hepatitis (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e12.482\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e8.060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e19.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e7.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e3.358\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e14.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eFibrosis (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e2.385\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e3.792\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e1.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.482\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.603\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e2.919\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eBallooning degeneration (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e1.449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.555\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e3.786\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e4.076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e17.769\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 138px;\"\u003e\n \u003cp\u003eConstant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 66px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e_\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur 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(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eHistopathological 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 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Notably, cirrhosis was significantly more common in female patients (p\u0026thinsp;=\u0026thinsp;0.002), a finding warranting further investigation, although a few studies have reported different sex-based trends in chronic liver injury progression(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDetecting 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\u0026rsquo;s disease. These conditions often develop early scarring in the liver that cannot be clearly seen with imaging or blood tests alone(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In our study, Wilson\u0026rsquo;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.\u003c/p\u003e\u003cp\u003eOne 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.\u003c/p\u003e\u003cp\u003eThe 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(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe 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(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe 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(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). 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(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). This also aligns with our study, as a considerable proportion of patients in our study also presented with jaundice and organomegaly.\u003c/p\u003e\u003cp\u003eIn 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\u0026mdash;thus, liver biopsy remains the gold standard(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). This is also consistent with our study, in which liver biopsy was considered the gold standard for a definite diagnosis.\u003c/p\u003e\u003cp\u003eAccordingly, 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.\u003c/p\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eSome 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\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis 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.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003eAST = Aspartate Aminotransferase\u003c/li\u003e\n \u003cli\u003eALT = Alanine Aminotransferase\u003c/li\u003e\n \u003cli\u003eALP = Alkaline Phosphatase\u003c/li\u003e\n \u003cli\u003eINR = International Normalized Ratio\u003c/li\u003e\n \u003cli\u003eSD = Standard Deviation\u003c/li\u003e\n \u003cli\u003eSPSS = Statistical Package for the Social Sciences\u003c/li\u003e\n \u003cli\u003eCI = Confidence Interval\u003c/li\u003e\n \u003cli\u003eOR = Odds Ratio\u003c/li\u003e\n \u003cli\u003eCl 95% = 95% Confidence Interval\u003c/li\u003e\n \u003cli\u003eU/L = Units per Liter\u003c/li\u003e\n \u003cli\u003eg/dL = grams per deciliter\u003c/li\u003e\n \u003cli\u003emg/dL = milligrams per deciliter\u003c/li\u003e\n \u003cli\u003eGSD = Glycogen Storage Disease\u003c/li\u003e\n \u003cli\u003eMRI = Magnetic Resonance Imaging\u003c/li\u003e\n \u003cli\u003eESPGHAN = European Society for Paediatric Gastroenterology, Hepatology and Nutrition\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate Approved by Ethics Committee of the School of Medicine,\u0026nbsp;ShahidBeheshtiUniversity \u0026nbsp;of medical sciences number)\u0026nbsp;IR.SBMU.MSP.REC.1401.575) \u0026nbsp;Written informed consent obtained from all participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest related to the design, conduct, or reporting of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAH conceived the study; NA collected data; MH \u0026amp;NG analyzed data; all authors contributed to writing and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe 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\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKalra A, Yetiskul E, Wehrle CJ, Tuma F. Physiology, Liver. StatPearls. Treasure Island (FL)2025.\u003c/li\u003e\n\u003cli\u003eArya G, Balistreri WF. Pediatric liver disease in the United States: epidemiology and impact. J Gastroenterol Hepatol. 2002;17(5):521-5.\u003c/li\u003e\n\u003cli\u003eSardar A, Sr., Parkash A, Merchant AA, Qamar B, Ayub F, Zehravi S. Etiology in Children Presented With Chronic Liver Disease in a Tertiary Care Hospital. Cureus. 2022;14(6):e25570.\u003c/li\u003e\n\u003cli\u003eDhawan A. Etiology and prognosis of acute liver failure in children. Liver Transpl. 2008;14 Suppl 2:S80-4.\u003c/li\u003e\n\u003cli\u003eFang Y, Yu J, Lou J, Peng K, Zhao H, Chen J. Clinical and Genetic Spectra of Inherited Liver Disease in Children in China. Front Pediatr. 2021;9:631620.\u003c/li\u003e\n\u003cli\u003eZou YG, Wang H, Li WW, Dai DL. Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders. World J Gastroenterol. 2023;29(14):2114-26.\u003c/li\u003e\n\u003cli\u003eMarginean CO, Melit LE, Sasaran MO. Metabolic Associated Fatty Liver Disease in Children-From Atomistic to Holistic. Biomedicines. 2021;9(12).\u003c/li\u003e\n\u003cli\u003ePinto RB, Schneider AC, da Silveira TR. Cirrhosis in children and adolescents: An overview. World J Hepatol. 2015;7(3):392-405.\u003c/li\u003e\n\u003cli\u003eGiannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005;172(3):367-79.\u003c/li\u003e\n\u003cli\u003ePandey N, Hoilat GJ, John S. Liver Biopsy. StatPearls. Treasure Island (FL)2025.\u003c/li\u003e\n\u003cli\u003eAlswat KA, Mumtaz K, Jafri W. Liver biopsy for histological assessment: The case in favor. Saudi J Gastroenterol. 2010;16(2):133-9.\u003c/li\u003e\n\u003cli\u003eCovelli C, Sacchi D, Sarcognato S, Cazzagon N, Grillo F, Baciorri F, et al. Pathology of autoimmune hepatitis. Pathologica. 2021;113(3):185-93.\u003c/li\u003e\n\u003cli\u003eJohncilla M, Mitchell KA. Pathology of the liver in copper overload. Semin Liver Dis. 2011;31(3):239-44.\u003c/li\u003e\n\u003cli\u003eLitchfield IJ, Lilford RJ, Bentham LM, Greenfield SM. A qualitative exploration of the motives behind the decision to order a liver function test in primary care. Qual Prim Care. 2014;22(4):201-10.\u003c/li\u003e\n\u003cli\u003eAzizaddini S, Mani N. Liver Imaging. StatPearls. Treasure Island (FL)2025.\u003c/li\u003e\n\u003cli\u003eSun C, Zhao X, Shi L, Fan X, Qi X. Distinct ways to perform a liver biopsy: The core technique setups and updated understanding of these modalities. Endosc Ultrasound. 2023;12(6):437-44.\u003c/li\u003e\n\u003cli\u003eNeuberger J, Patel J, Caldwell H, Davies S, Hebditch V, Hollywood C, et al. Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology. Gut. 2020;69(8):1382-403.\u003c/li\u003e\n\u003cli\u003eDezsofi A, Baumann U, Dhawan A, Durmaz O, Fischler B, Hadzic N, et al. Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee. J Pediatr Gastroenterol Nutr. 2015;60(3):408-20.\u003c/li\u003e\n\u003cli\u003eSosnowska-Sienkiewicz P, Miedziarek C, Danielewicz D, Mankowski P. Liver biopsies in children indications, techniques, results and complications. A single-centre study. Pol Przegl Chir. 2022;95(4):1-5.\u003c/li\u003e\n\u003cli\u003eGovender P, Jonas MM, Alomari AI, Padua HM, Dillon BJ, Landrigan-Ossar MF, et al. Sonography-guided percutaneous liver biopsies in children. AJR Am J Roentgenol. 2013;201(3):645-50.\u003c/li\u003e\n\u003cli\u003eForna L, Bozomitu L, Lupu VV, Lupu A, Trandafir LM, Adam Raileanu A, et al. Pediatric Perspectives on Liver Cirrhosis: Unravelling Clinical Patterns and Therapeutic Challenges. J Clin Med. 2024;13(14).\u003c/li\u003e\n\u003cli\u003eLu M, Li J, Zhou Y, Rupp LB, Moorman AC, Spradling PR, et al. Trends in Cirrhosis and Mortality by Age, Sex, Race, and Antiviral Treatment Status Among US Chronic Hepatitis B Patients (2006-2016). J Clin Gastroenterol. 2022;56(3):273-9.\u003c/li\u003e\n\u003cli\u003eRubin JB, Sundaram V, Lai JC. Gender Differences Among Patients Hospitalized With Cirrhosis in the United States. J Clin Gastroenterol. 2020;54(1):83-9.\u003c/li\u003e\n\u003cli\u003eBerumen J, Baglieri J, Kisseleva T, Mekeel K. Liver fibrosis: Pathophysiology and clinical implications. WIREs Mech Dis. 2021;13(1):e1499.\u003c/li\u003e\n\u003cli\u003eOzdogan E, Arikan C. Liver fibrosis in children: a comprehensive review of mechanisms, diagnosis, and therapy. Clin Exp Pediatr. 2023;66(3):110-24.\u003c/li\u003e\n\u003cli\u003eKhalifa A, Lewin DN, Sasso R, Rockey DC. The Utility of Liver Biopsy in the Evaluation of Liver Disease and Abnormal Liver Function Tests. Am J Clin Pathol. 2021;156(2):259-67.\u003c/li\u003e\n\u003cli\u003eLee TH, Kim WR, Poterucha JJ. Evaluation of elevated liver enzymes. Clin Liver Dis. 2012;16(2):183-98.\u003c/li\u003e\n\u003cli\u003eOvchinsky N, Moreira RK, Lefkowitch JH, Lavine JE. Liver biopsy in modern clinical practice: a pediatric point-of-view. Adv Anat Pathol. 2012;19(4):250-62.\u003c/li\u003e\n\u003cli\u003ePragati Aditya Sathe DEM. Pediatric Liver Biopsy: A Clinicopathologic Study. Annals of pathology and lab medicine. 2017;4(4).\u003c/li\u003e\n\u003cli\u003eDiana Luc\u0026iacute;a Mart\u0026iacute;nez Baquero LEJB. Liver Biopsy in Children Under 5 Years Experience in a Colombian Pediatric Hospital. Revista colombiana de Gastroenterolog\u0026iacute;a. 2015;30(1).\u003c/li\u003e\n\u003cli\u003eMedynska-Przeczek A, Stochel-Gaudyn A, Wedrychowicz A. Liver fibrosis assessment in pediatric population - can ultrasound elastography be an alternative method to liver biopsy? A systematic review. Adv Med Sci. 2024;69(1):8-20.\u003c/li\u003e\n\u003cli\u003eEngelmann G, Quader J, Teufel U, Schenk JP. Limitations and opportunities of non-invasive liver stiffness measurement in children. World J Hepatol. 2017;9(8):409-17.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7617977/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7617977/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eLiver 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.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective cross-sectional study was conducted on 1,158 patients under 18 years of age who underwent liver biopsy at Mofid Children\u0026rsquo;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.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eUltrasound-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.\u0026nbsp;1: \u003cb\u003edistribution of common pathological findings\u003c/b\u003e). Non-specific changes (252, 21.8%), metabolic liver disease (170, 14.7%), and Wilson\u0026rsquo;s disease (108, 9.3%) were the most common diagnoses (Fig.\u0026nbsp;3: \u003cb\u003ecommon CLINICAL CONDITIONS\u003c/b\u003e). 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\u0026thinsp;=\u0026thinsp;0.002). Statistically significant associations were observed between biopsy type and specific histopathological findings (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cb\u003eTables\u0026nbsp;2 \u0026amp; 3\u003c/b\u003e).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eDespite 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.\u003c/p\u003e","manuscriptTitle":"Pediatric Liver Biopsies Over a Decade: Patterns of Disease and Biochemical Associations","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-03 18:52:41","doi":"10.21203/rs.3.rs-7617977/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14105c40-2a91-4dbe-b46e-3bd487247eee","owner":[],"postedDate":"October 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T14:41:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-03 18:52:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7617977","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7617977","identity":"rs-7617977","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}