Adequacy criteria of Tru-cut needle liver biopsy in neonatal cholestasis

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The decrease in SRSF3 levels results in an alternative splicing event within the SRSF1 gene producing an isoform that undergoes nonsense-mediated decay. This results in a decreased in SRSF1 expression. Low expression of SRSF1 in the nucleus produces a variety of alterations in the splicing events among which that of the tumor suppressor Kruppel-like factor 6 (KLF6), enhancing the splicing pattern SV1 isoform <a class="elsevierStyleCrossRef" href="#bib0066">[66]</a>, which leads to increased cell proliferation as it antagonizes the ability of wild-type KLF6 to suppress it." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Marco Baralle, Francisco. E. Baralle" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Marco" "apellidos" => "Baralle" ] 1 => array:2 [ "nombre" => "Francisco. E." "apellidos" => "Baralle" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268121002337?idApp=UINPBA00004N" "url" => "/16652681/000000260000000C/v5_202208200714/S1665268121002337/v5_202208200714/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Adequacy criteria of Tru-cut needle liver biopsy in neonatal cholestasis" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Behairy El-Sayed Behairy, Alif Abd El-Hakim Allam, Shymaa Galal Hegazy, Doha Maher Taie, Ahmad Mohamed Sira" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Behairy El-Sayed" "apellidos" => "Behairy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] ] ] 1 => array:3 [ "nombre" => "Alif Abd El-Hakim" "apellidos" => "Allam" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] ] ] 2 => array:3 [ "nombre" => "Shymaa Galal" "apellidos" => "Hegazy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] ] ] 3 => array:3 [ "nombre" => "Doha Maher" "apellidos" => "Taie" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0002" ] ] ] 4 => array:4 [ "nombre" => "Ahmad Mohamed" "apellidos" => "Sira" "email" => array:1 [ 0 => "asira@liver.menofia.edu.eg" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0001" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pediatric Hepatology, Gastroenterology, and Nutrition, National Liver Institute, Menoufia University, 32511 Shebin El-Koom, Menoufia, Egypt" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Department of Pathology, National Liver Institute, Menoufia University, 32511 Shebin El-Koom, Menoufia, Egypt" "etiqueta" => "b" "identificador" => "aff0002" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0003" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3392 "Ancho" => 2333 "Tamanyo" => 763835 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Fig 3&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Summary diagram for comparing different core lengths for every pathological item assessed together with the activity grade and fibrosis stage. For example, the box summarizing the fibrosis stage assessment results showed that the 4-mm core length reported a fibrosis stage lower than that reported by the 6-mm core length. However, the fibrosis stages reported by the core lengths of 6, 8, 10, and 12 mm showed no significant differences among them. Therefore, the adequate core length for reporting the fibrosis stage was 6 mm." ] ] ] "textoCompleto" => "1IntroductionLiver biopsy is a cornerstone in the diagnostic workup of many disorders causing neonatal cholestasis (NC). However, sampling errors with insufficient liver specimens could cause a biased pathological diagnosis even with expert pathologists. Given the neonatal liver's nonspecific pathological response to different etiologies, there are overlaps in various disease pathologies <a class="elsevierStyleCrossRef" href="#bib0001">[1]</a>. This makes it challenging to define the specific etiology by pathological evaluation.Moreover, as an invasive procedure with some risks, a sample with good quality that could lead to the correct diagnosis should be acquired to balance this potential risk. This means that the biopsy should be of sufficient size to view a representative amount of parenchyma and the number of complete portal tracts (CPTs). Even a very small biopsy specimen may be enough to establish a diagnosis when the disease's key lesion is present <a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>.Many studies have defined adequate liver biopsy criteria in those with diffuse pathology in adults <a class="elsevierStyleCrossRef" href="#bib0003">[3]</a>. However, no previous studies have defined the adequacy criteria of liver biopsy samples in NC. In the present study, we aimed to determine adequate liver biopsy sample characteristics in NC regarding the core length and portal tract numbers.2Materials and methods2.1Study populationThis retrospective study included 58 specimens of liver tissue from infants with NC. All liver specimens of infants with NC admitted to the Department of Pediatric Hepatology, Gastroenterology, and Nutrition who underwent liver biopsy from July 1, 2016, to June 30, 2017, were collected. Within the study duration, 62 infants with NC underwent liver biopsy. Four cases were excluded due to core fragmentation (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>).<elsevierMultimedia ident="fig0001"></elsevierMultimedia>In compliance with the 1975 Declaration of Helsinki and its later amendments, this study's approval was obtained from the Research Ethics Committee of the National Liver Institute. This manuscript does not contain any content that can reveal the patients’ identities; therefore, written informed consent was not obtained from the guardians.2.2Liver biopsy sampling and processingAll liver biopsy specimens were previously obtained through a Tru-cut needle 16-gauge (G) by ultrasound guidance with one needle pass. After processing of the liver tissue, sections were stained with hematoxylin and eosin, diastase periodic acid-Schiff, orcein, and Masson's trichrome stains for routine histopathological evaluation. The core lengths of all samples after fixation and staining were measured. They ranged from 4 mm to 12 mm. The core lengths were as follows: eight samples, 12 mm; fifteen samples, 10 mm; nineteen samples, 8 mm; nine samples, 6 mm; and seven samples, 4 mm (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>).For each core of liver tissue with a length >4 mm, serial shortening by 2 mm was performed until reaching the 4-mm core length. Accordingly, we acquired the following core lengths: 58 samples with a core length of 4 mm, 51 samples with a core length of 6 mm, 42 samples with a core length of 8 mm, 23 samples with a core length of 10 mm, and eight samples with a core length of 12 mm (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>).2.3Assessment of adequacy criteriaAn adequate sample is a liver tissue specimen that can express the different pathological criteria without difference from the larger samples. To assess adequacy, we considered the pathological criteria defined by the largest core size as the internal reference standard. Determining the etiological diagnosis was out of the scope of this study in the determination of the adequacy criteria. We relied on defining adequacy to determine the adequate core length and CPT number, while width was that of the 16 G Tru-cut needle.The current study design of serial shortening of samples to assess the adequacy criteria has been performed before in adults’ studies by Colloredo et al. <a class="elsevierStyleCrossRef" href="#bib0004">[4]</a>. In the present work, we compared the pathological scores reported by the smallest available core length (4 mm) to those reported by the next largest core length (6 mm) to define the adequate core length. Then, we compared the 6-mm core length to the 8-mm core length to reach the largest available core length (12 mm). The smallest core length that could define the pathological scores with no significant difference from those reported by the larger core lengths was considered adequate.The CPT numbers of the defined adequate core length were reported, and the mean values were considered in the definition of the criteria of the adequate liver biopsy core. However, the width was standardized to the width of the liver biopsy cores obtained by the Tru-cut needle 16 G. It was not feasible to obtain different widths for comparison.2.4Histopathological evaluationFor each liver section, definite pathological parameters were recorded and summed into two items: activity grade (score: 0-15) and fibrosis stage (score: 0-4). The activity grade included the following nine pathological items we reported previously <a class="elsevierStyleCrossRef" href="#bib0005">[5]</a>: (1) bile ductular proliferation, (2) bile plugs, (3) portal infiltrate with lymphocytes, (4) neutrophils, and (5) eosinophils, (6) giant cell transformation of hepatocytes, (7) hepatocyte swelling, (8) rosette formation, and (9) extramedullary hematopoiesis. All reported items were given scores; higher scores indicate a greater possibility of biliary atresia rather than nonbiliary atresia cholestasis <a class="elsevierStyleCrossRef" href="#bib0006">[6]</a> (<a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>).<elsevierMultimedia ident="tbl0001"></elsevierMultimedia>Liver fibrosis was classified into five stages <a class="elsevierStyleCrossRef" href="#bib0007">[7]</a>, as reported in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>. Two senior pathologists interpreted all histopathological findings. All pathological criteria were assessed three times, one month apart, and median values were reported. The intra- and interobserver kappa values for different pathological parameters were 0.865–0.932 and 0.813–0.842, respectively. For the histopathological findings that showed no concordance between the two pathologists, a shared reassessment was performed.2.5Statistical analysisQuantitative data are expressed as the mean ± standard deviation. Kendall's coefficient of concordance was used to assess agreement among different core lengths. It was done on two-by-two comparisons and didn't compare all biopsy lengths at the same time. This test results in a number that varies from 0 (complete disagreement) to 1 (complete agreement) <a class="elsevierStyleCrossRef" href="#bib0008">[8]</a>. We also performed one-way analysis of variance (ANOVA) to analyze differences in the means of the dependent variable (score) when stratified by the levels of the independent variable (biopsy length). The kappa coefficient was calculated to measure the intra- and interobserver agreements. A P-value of < 0.05 was used to indicate statistically significant results. SPSS 21.0 (SPSS Inc., Chicago, IL, USA) was used to perform the statistical analysis.Results3Adequate core length for the NC activity3.1Adequacy criteria for the activity gradeBy serial comparison of the activity score reported by the 4-mm core length to that reported by the larger core length and so on, it was found that the 4-mm core length was concordant with the 6-mm core length, P = 0.257 and W=0.988. The 6-mm core length was concordant with the 8 mm core length, P = 0.180 and W=0.966. The 8-mm core length was concordant with the 10-mm core length, P = 1.0 and W=1.0. Finally, the 10-mm core length was concordant with the 12-mm core length, P = 1.0 and W=1.0. Therefore, the adequate core length for reporting the total activity grade of NC was 4 mm (<a class="elsevierStyleCrossRef" href="#fig0002">Fig. 2</a>).<elsevierMultimedia ident="fig0002"></elsevierMultimedia>3.2Adequacy criteria for individual parameters of NC activityBy serial comparisons of different core lengths for every individual histopathological parameter of NC activity, it was found that the 4-mm core length showed concordance with the larger core lengths (P > 0.05 and W=0.966-1.0, for all). Therefore, the adequate core length for the individual parameters of NC activity was 4 mm. <a class="elsevierStyleCrossRef" href="#fig0003">Fig. 3</a> summarizes the results of the comparison of different core lengths for every histopathological parameter.<elsevierMultimedia ident="fig0003"></elsevierMultimedia>4Adequate core length for the NC fibrosis stageConversely, serial comparison of core lengths to define the adequate length for fibrosis assessment showed no concordance between the 4-mm core length and the 6-mm core length (P=0.014 and W=0.598). In contrast, there was concordance between serial core lengths of 6, 8, 10, and 12 mm (P>0.05 and W=0.99-1.0, for all). Therefore, the fibrosis stage assessment's adequate core length was 6 mm (<a class="elsevierStyleCrossRef" href="#fig0003">Fig.s 3</a> and <a class="elsevierStyleCrossRef" href="#fig0004">4</a>).<elsevierMultimedia ident="fig0004"></elsevierMultimedia>5Adequate complete portal tract number for NC activity and fibrosis stageThe 4-mm core lengths were found to have a CPT number of 8 ± 3. Therefore, the adequate CPT number for reporting activity grade ranged from 5 to 11 per core.The 6-mm core lengths were found to have a CPT number of 11 ± 3. Therefore, the adequate CPT numbers for reporting the fibrosis stage ranged from 8 to 14 per core.6ANOVA resultsANOVA of all examined histopathological parameters revealed comparable results to those of Kendall's coefficient of concordance. Moreover, Kendall's coefficient test had the benefit of considering the related-samples concordance and presenting the continuous field information, as shown in <a class="elsevierStyleCrossRef" href="#fig0002">Figs. 2</a> and <a class="elsevierStyleCrossRef" href="#fig0004">4</a>. P-values derived from the ANOVA of the studied parameters were as follows: activity grade=0.17, bile ductular proliferation=0.560, bile plugs=0.810, lymphocyte infiltrate=0.910, neutrophil infiltrate=0.894, eosinophil infiltrate=0.913, giant cells=0.543, hepatocyte swelling=0.506, rosette formation=0.860, extramedullary hematopoiesis=0.992, and fibrosis stage=0.685.7DiscussionDespite progress in investigational tools and innovative imaging techniques, liver biopsy remains vital in diagnosing many pediatric liver disorders. An adequate sample should be obtained to avoid misdiagnosis as a consequence of sampling errors. The American Association for the Study of Liver Diseases recommended the importance of a sufficient sample size to correctly diagnose diffuse liver disorders <a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>. Many studies in adults concluded that the smaller the liver sample was, the less accurate the assessment of both the grade of activity and the stage of fibrosis of diffuse liver disorders <a class="elsevierStyleCrossRef" href="#bib0004">[4]</a>,<a class="elsevierStyleCrossRef" href="#bib0009">[9]</a>.Optimal biopsy length is the subject of debate because an accurate diagnosis of some diseases can be made with short samples. Studies in patients with viral hepatitis have shown that grading and staging accuracy is reduced in biopsies less than 2.0 cm in length <a class="elsevierStyleCrossRef" href="#bib0009">[9]</a>.To the best of our knowledge, no studies have evaluated Tru-cut needle liver biopsy adequacy criteria in infants with liver diseases. Data from the adult literature recommend using a 16 G needle and a biopsy length of 2 to 3 cm to ensure adequate biopsy. These defined adequacy criteria allow for more straightforward pathological evaluations with more significant numbers of CPTs visualized than the 18 G needle <a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>.The present study revealed that a 4-mm core length is an adequate core length for NC activity grade assessment. It has been shown that this core length gives the same histopathological scores for activity grade as those reported by the larger core lengths of 6, 8, 10, and 12 mm (the highest core length). Moreover, the adequate CPT number for assessing the NC activity grade was found to be 8±3.In the liver fibrosis assessment, to determine the size of an adequate liver biopsy, the variability of the liver fibrosis distribution within the liver for the particular disease must be known, which is likely to change with the disease stage. Adequate biopsy samples need to be considered in light of the degree to which small inadequate biopsies tend to underestimate both disease grade and stage <a class="elsevierStyleCrossRef" href="#bib0010">[10]</a>.The present study revealed that the 6-mm core length is the adequate core length for reporting the fibrosis stage. This core length showed concordance with the fibrosis stages reported by the larger core lengths of 8, 10, and 12 mm (the highest core length). Additionally, the adequate CPT number for assessing the NC fibrosis stage was found to be 11 ±3.The larger core length required for assessing the NC fibrosis stage than that needed for evaluating the NC activity grade follows the previous recommendation that adequate liver biopsy would be larger when there is a need to assess the stage of fibrosis. Moreover, if cirrhosis is suspected, a cutting rather than a suction needle is recommended <a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>.Colloredo et al. <a class="elsevierStyleCrossRef" href="#bib0004">[4]</a> evaluated the effects of core length and width on the grading and staging of diffuse liver pathology. The methodology consisted of progressively reducing the original samples’ length and width, all at least 2.5-3 cm long. Their study provided evidence that both the length and the width of the biopsy core affect the grading and staging and that examining shorter and thinner samples leads to underestimating disease severity. The result was that a 20-mm length is the ‘minimum’ recommended size of a liver biopsy containing a number of CPTs ≥11 for the histological assessment of activity and fibrosis in chronic viral hepatitis in adults.The American Association for the Study of Liver Diseases guidelines recommended that a biopsy of at least 2-3 cm in length, 11 CPT, and 16 G in caliber is recommended for the accurate diagnosis, grading, and staging of fibrosis in diffuse liver disorders in adults <a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>.The use of liver biopsy guidelines in clinical practice from the Royal College of Pathology, British Society of Gastroenterology, and the Royal College of Radiologists recommended that a 16 G needle be used for the percutaneous approach. However, an 18 G needle should be used for percutaneous biopsy of a solid lesion, and the length of the sample should be ≥20 mm <a class="elsevierStyleCrossRef" href="#bib0003">[3]</a>.The Royal College of Pathologists published its first guidelines on liver biopsy in 2008 and updated its guidelines in 2014 to suggest minimum adequacy requirements for samples to be at least 10 mm long and to contain six portal tracts <a class="elsevierStyleCrossRef" href="#bib0011">[11]</a>. These guidelines have now been revised to ensure that all recommendations are up to date. In the third set of guidelines published in 2020 state that if the liver biopsy is adequate, it should be at least 20 mm in length obtained by a 16 G needle and contain at least ten CPTs. A biopsy of less than 10 mm is of limited diagnostic value, and a second pass should be considered. If the biopsy core is between 10 and 20 mm in length, the diagnosis may be compromised. A second pass should be considered, especially if the biopsy's main indications are staging fibrosis <a class="elsevierStyleCrossRef" href="#bib0012">[12]</a>.Although adult studies have recommended a biopsy length of 20 mm, the adequacy of a smaller sample size was apparent in the present study. This difference could be attributed to some technical factors. The ratio of the obtained sample to the relatively smaller infant liver approximates the ratio used in adults. Moreover, this difference could be due to the use of core-aspiration needles, such as Menghini needles, in some adult studies<a class="elsevierStyleCrossRef" href="#bib0003">[3]</a>,<a class="elsevierStyleCrossRef" href="#bib0004">[4]</a>, which are less traumatizing and can allow for the acquisition of a longer core than the Tru-cut needle used in our study. On the other hand, Menghini needles were avoided, in our study, because the samples obtained tend to be more fragmented. Some adult studies used more than one pass to acquire the target core length<a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>,<a class="elsevierStyleCrossRef" href="#bib0013">[13]</a>. We avoided multiple needle passes in the present study to decrease the biopsy-related complications associated with multiple passes <a class="elsevierStyleCrossRef" href="#bib0002">[2]</a>.Understanding the differences between the liver pathology in neonates and infants from those in adults explains the differences in liver specimen adequacy criteria between pediatric patients and adults. Application of the adequacy criteria reported in adults would miss the diagnosis in many neonates and infants who could be accurately diagnosed with smaller specimens than those defined from adult studies.A limitation of this study is the retrospective nature, which could not permit a comparison between different needle sizes: 16 G vs. 18 G. Meanwhile, it was challenging to acquire different widths from the studied cores in the present study. However, in our center, we routinely use Tru-cut needles 16 G because our former 18 G needles yielded fragmented tissue samples with fewer CPT numbers. Palmer et al. <a class="elsevierStyleCrossRef" href="#bib0013">[13]</a> reported that specimen adequacy was not significantly affected by the biopsy gauge of 16 G vs. 18 G. However, other studies reported that 16 G needles yielded better quality samples with a higher CPT number than 18 G needles [<a class="elsevierStyleCrossRef" href="#bib0013">13</a>, <a class="elsevierStyleCrossRef" href="#bib0014">14</a>].In conclusion, to the best of our knowledge, the present work is the first to assess liver biopsy sample adequacy criteria for the accurate assessment of neonatal liver disorders, namely, NC. A liver specimen acquired with a 16 G Tru-cut needle with a 4-mm length and a CPT of 5-11 is accurate for activity grading. However, to stage fibrosis for NC, a 16 G Tru-cut needle sample should be at least 6 mm in length with CPT numbers of 8-14.Financial supportThis study was funded by the National Liver Institute, Menoufia University, Egypt. The funders had no particular role in the study design, recruitment of individuals, data analysis, or writing of the report.Author contributionsBehairy BE, Allam AA, Hegazy SG, Taie DM, and Sira AM were involved in the study concept and design; Behairy BE, Allam AA, Hegazy SG, and Sira AM were involved in the recruitment of patients, clinical management and follow-up and data acquisition; Taie DM performed the histopathological examination; Sira A performed the statistical analysis and designed the figures; Behairy BE, Allam AA, and Sira AM performed data interpretation; Behairy BE, Allam AA, Taie DM, and Sira AM wrote the manuscript; all the authors reviewed the manuscript and ultimately approved it for submission." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1761530" "titulo" => "Highlights" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abss0001" ] ] ] 1 => array:3 [ "identificador" => "xres1761531" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abss0002" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1549127" "titulo" => "Keywords" ] 3 => array:2 [ "identificador" => "xpalclavsec1549126" "titulo" => "Abbreviations" ] 4 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0002" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0003" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0004" "titulo" => "Liver biopsy sampling and processing" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Assessment of adequacy criteria" ] 3 => array:2 [ "identificador" => "sec0006" "titulo" => "Histopathological evaluation" ] 4 => array:2 [ "identificador" => "sec0007" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0008" "titulo" => "Adequate core length for the NC activity" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0009" "titulo" => "Adequacy criteria for the activity grade" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Adequacy criteria for individual parameters of NC activity" ] ] ] 7 => array:2 [ "identificador" => "sec0011" "titulo" => "Adequate core length for the NC fibrosis stage" ] 8 => array:2 [ "identificador" => "sec0012a" "titulo" => "Adequate complete portal tract number for NC activity and fibrosis stage" ] 9 => array:2 [ "identificador" => "sec0013" "titulo" => "ANOVA results" ] 10 => array:2 [ "identificador" => "sec0014" "titulo" => "Discussion" ] 11 => array:2 [ "identificador" => "sec0016" "titulo" => "Financial support" ] 12 => array:2 [ "identificador" => "sec0012" "titulo" => "Author contributions" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-01-29" "fechaAceptado" => "2021-03-03" "PalabrasClave" => array:1 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1549127" "palabras" => array:5 [ 0 => "Adequacy criteria" 1 => "Infants" 2 => "Liver biopsy" 3 => "Neonatal cholestasis" 4 => "Tru-cut needle" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1549126" "palabras" => array:4 [ 0 => "CPT" 1 => "CPTs" 2 => "G" 3 => "NC" ] ] ] ] "tieneResumen" => true "highlights" => array:2 [ "titulo" => "Highlights" "resumen" => "<ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001">•Liver biopsy remains a cornerstone in the assessment of diffuse liver diseases.</li><li class="elsevierStyleListItem" id="celistitem0002">•Defining adequacy criteria for liver specimens avoids the impact of sampling errors.</li><li class="elsevierStyleListItem" id="celistitem0003">•Many studies have defined adequacy criteria of adult liver biopsy; however, it is the first study that assesses the adequacy criteria in neonatal cholestasis (NC).</li><li class="elsevierStyleListItem" id="celistitem0004">•A core length of 4 mm with a complete portal tract number (CPT) of 8±3 is considered adequate for NC activity assessment.</li><li class="elsevierStyleListItem" id="celistitem0005">•A core length of 6 mm with a CPT number of 11±3 is required to assess the fibrosis stage adequately in NC.</li></ul>" ] "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Introduction and Objectives: Assessment of liver biopsy sample adequacy criteria is essential to avoid sampling errors in patients with diffuse liver pathology. Many studies have evaluated these criteria in adults; however, no previous studies have been performed on neonatal liver disorders. We aimed to assess the adequacy criteria of Tru-cut needle liver biopsy samples in infants with neonatal cholestasis (NC). Methods: In a retrospective analysis of infants who underwent liver biopsy for NC within a one-year duration, 58 specimens were recruited. The core lengths after fixation were measured. All samples were acquired with a 16-gauge (G) Tru-cut needle. Serial shortening of these samples was performed to define the smallest core length that gives representative parenchyma that could determine the activity grade and fibrosis stage reported by larger cores. Results: It was found that a 4-mm core length with a complete portal tract (CPT) number of 8±3 could adequately assess the NC activity grade. In addition, a 6-mm core length with a CPT number of 11±3 could adequately estimate NC fibrosis stage. Conclusions: The adequacy criteria of liver tissue samples for the accurate assessment of NC are different from those defined for adult diffuse liver pathology. At least a 4-mm core length with a CPT number of 8±3 and a 6-mm core length with a CPT number of 11±3 acquired by a 16-G Tru-cut needle should be used to assess NC activity grade and fibrosis stage, respectively." ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2038 "Ancho" => 2750 "Tamanyo" => 408287 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig 1&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Flow chart of the included and excluded cases and the core lengths of the included specimens before and after serial shortening." ] ] 1 => array:8 [ "identificador" => "fig0002" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2202 "Ancho" => 2916 "Tamanyo" => 562423 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Fig 2&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Kendall's coefficient of concordance for the assessment of the adequate core length for the activity grade. A) Comparison between the activity reported by the core lengths of 4 and 6 mm, P=0.257. The upper diagram represents the activity scores reported for every core length. The lower diagram represents the ranked means and frequencies for every core length. B) Comparison between core lengths of 6 and 8 mm, P=0.180; C) Comparison between core lengths of 8 and 10 mm, P=1.0; D) Comparison between core lengths of 10 and 12 mm, P=1.0." ] ] 2 => array:8 [ "identificador" => "fig0003" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3392 "Ancho" => 2333 "Tamanyo" => 763835 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Fig 3&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Summary diagram for comparing different core lengths for every pathological item assessed together with the activity grade and fibrosis stage. For example, the box summarizing the fibrosis stage assessment results showed that the 4-mm core length reported a fibrosis stage lower than that reported by the 6-mm core length. However, the fibrosis stages reported by the core lengths of 6, 8, 10, and 12 mm showed no significant differences among them. Therefore, the adequate core length for reporting the fibrosis stage was 6 mm." ] ] 3 => array:8 [ "identificador" => "fig0004" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2382 "Ancho" => 3167 "Tamanyo" => 623530 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Fig 4&#58" "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Kendall's coefficient of concordance for the assessment of the adequate core length for the fibrosis stage. A) Comparison between the fibrosis stages reported by core lengths of 4 and 6 mm, P=0.014. The upper diagram represents the fibrosis stage reported for every core length. The lower diagram represents the ranked mean and frequency for every core length. B) Comparison between core lengths of 6 and 8 mm, P=1.0. C) Comparison between core lengths of 8 and 10 mm, P=0.317. D) Comparison between the core lengths of 10 and 12 mm, P=1.0." ] ] 4 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Table 1&#58" "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Histological findings and their grades \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0003"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Bile ductular proliferationNone: Average number of bile ductules per portal tract < 5Mild: Average number of bile ductules per portal tract between 5 to 9Moderate: Average number of bile ductules per portal tract ≥ 10Marked: Elongated, attenuated, angulated bile ductules in addition to proliferation (average number of bile ductules per portal tract ≥ 10) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0004"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0123 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0005"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Bile plug in portal ductulesAbsentPresent \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0007"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Lymphocytic infiltrate in portal regionNone (presence of lymphocytes up to 4 cells in the portal tract; normal resident lymphocytes)Mild (presence of large number of lymphocytes in the portal tract without presence of lymphoid aggregates)Moderate–marked (presence of large number of lymphocytes in the portal tract with presence of lymphoid aggregates) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">210 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Neutrophilic infiltrate in portal regionAbsent or mild (presence of few numbers around some bile ducts)Moderate-marked (presence of large numbers around some bile ducts) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0011"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Eosinophilic infiltrate in portal regionAbsent or mild (presence of few numbers around some bile ducts)Moderate-marked (presence of large numbers around some bile ducts) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Multinucleated hepatocytes (giant cells)NoneAround central veinDiffuse \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">210 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Hepatocellular swellingNoneMild/focalPeriportal/diffuse \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">210 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Rosette formationAbsentPresent \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Extramedullary hematopoiesisAbsentPresent \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Total NC activity score \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0023"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Grades of fibrosisGrade 0: absent or fibrous expansion of some portal areasGrade 1: fibrous expansion of most portal areasGrade 2: focal porto-portal bridgingGrade 3: marked bridgingGrade 4: cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">01234 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Total fibrosis stage score \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Neonatal cholestasis histopathological activity score and fibrosis stage" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "[1]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Histopathological features and accuracy for diagnosing biliary atresia by prelaparotomy liver biopsy in developing countries" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A Rastogi" 1 => "N Krishnani" 2 => "SK Yachha" 3 => "V Khanna" 4 => "U Poddar" 5 => "R. Lal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1440-1746.2008.05737.x" "Revista" => array:7 [ "tituloSerie" => "J Gastroenterol Hepatol" "fecha" => "2009" "volumen" => "24" "numero" => "1" "paginaInicial" => "97" "paginaFinal" => "102" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19196397" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0002" "etiqueta" => "[2]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver biopsy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "DC Rockey" 1 => "SH Caldwell" 2 => "ZD Goodman" 3 => "RC Nelson" 4 => "AD. Smith" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.22742" "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "2009" "volumen" => "49" "numero" => "3" "paginaInicial" => "1017" "paginaFinal" => "1044" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19243014" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0003" "etiqueta" => "[3]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "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" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J Neuberger" 1 => "J Patel" 2 => "H Caldwell" 3 => "S Davies" 4 => "V Hebditch" 5 => "C Hollywood" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/gutjnl-2020-321299" "Revista" => array:7 [ "tituloSerie" => "Gut" "fecha" => "2020" "volumen" => "69" "numero" => "8" "paginaInicial" => "1382" "paginaFinal" => "1403" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32467090" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0004" "etiqueta" => "[4]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G Colloredo" 1 => "M Guido" 2 => "A Sonzogni" 3 => "G. 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Behairy El-Sayed Behairya, Alif Abd El-Hakim Allama, Shymaa Galal Hegazya, Doha Maher Taieb, Ahmad Mohamed Siraa,

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asira@liver.menofia.edu.eg

Corresponding author.

a Department of Pediatric Hepatology, Gastroenterology, and Nutrition, National Liver Institute, Menoufia University, 32511 Shebin El-Koom, Menoufia, Egypt

b Department of Pathology, National Liver Institute, Menoufia University, 32511 Shebin El-Koom, Menoufia, Egypt

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          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Summary diagram for comparing different core lengths for every pathological item assessed together with the activity grade and fibrosis stage&#46; For example&#44; the box summarizing the fibrosis stage assessment results showed that the 4-mm core length reported a fibrosis stage lower than that reported by the 6-mm core length&#46; However&#44; the fibrosis stages reported by the core lengths of 6&#44; 8&#44; 10&#44; and 12 mm showed no significant differences among them&#46; Therefore&#44; the adequate core length for reporting the fibrosis stage was 6 mm&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="cesectitle0006">Introduction</span><p id="para0010" class="elsevierStylePara elsevierViewall">Liver biopsy is a cornerstone in the diagnostic workup of many disorders causing neonatal cholestasis &#40;NC&#41;&#46; However&#44; sampling errors with insufficient liver specimens could cause a biased pathological diagnosis even with expert pathologists&#46; Given the neonatal liver&#39;s nonspecific pathological response to different etiologies&#44; there are overlaps in various disease pathologies <a class="elsevierStyleCrossRef" href="#bib0001">&#91;1&#93;</a>&#46; This makes it challenging to define the specific etiology by pathological evaluation&#46;</p><p id="para0011" class="elsevierStylePara elsevierViewall">Moreover&#44; as an invasive procedure with some risks&#44; a sample with good quality that could lead to the correct diagnosis should be acquired to balance this potential risk&#46; This means that the biopsy should be of sufficient size to view a representative amount of parenchyma and the number of complete portal tracts &#40;CPTs&#41;&#46; Even a very small biopsy specimen may be enough to establish a diagnosis when the disease&#39;s key lesion is present <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a>&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">Many studies have defined adequate liver biopsy criteria in those with diffuse pathology in adults <a class="elsevierStyleCrossRef" href="#bib0003">&#91;3&#93;</a>&#46; However&#44; no previous studies have defined the adequacy criteria of liver biopsy samples in NC&#46; In the present study&#44; we aimed to determine adequate liver biopsy sample characteristics in NC regarding the core length and portal tract numbers&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="cesectitle0007az">Materials and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0008">Study population</span><p id="para0013" class="elsevierStylePara elsevierViewall">This retrospective study included 58 specimens of liver tissue from infants with NC&#46; All liver specimens of infants with NC admitted to the Department of Pediatric Hepatology&#44; Gastroenterology&#44; and Nutrition who underwent liver biopsy from July 1&#44; 2016&#44; to June 30&#44; 2017&#44; were collected&#46; Within the study duration&#44; 62 infants with NC underwent liver biopsy&#46; Four cases were excluded due to core fragmentation &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46;&#160;1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0014" class="elsevierStylePara elsevierViewall">In compliance with the 1975 Declaration of Helsinki and its later amendments&#44; this study&#39;s approval was obtained from the Research Ethics Committee of the National Liver Institute&#46; This manuscript does not contain any content that can reveal the patients&#8217; identities&#59; therefore&#44; written informed consent was not obtained from the guardians&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="cesectitle0009">Liver biopsy sampling and processing</span><p id="para0015" class="elsevierStylePara elsevierViewall">All liver biopsy specimens were previously obtained through a Tru-cut needle 16-gauge &#40;G&#41; by ultrasound guidance with one needle pass&#46; After processing of the liver tissue&#44; sections were stained with hematoxylin and eosin&#44; diastase periodic acid-Schiff&#44; orcein&#44; and Masson&#39;s trichrome stains for routine histopathological evaluation&#46; The core lengths of all samples after fixation and staining were measured&#46; They ranged from 4 mm to 12 mm&#46; The core lengths were as follows&#58; eight samples&#44; 12 mm&#59; fifteen samples&#44; 10 mm&#59; nineteen samples&#44; 8 mm&#59; nine samples&#44; 6 mm&#59; and seven samples&#44; 4 mm &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46;&#160;1</a>&#41;&#46;</p><p id="para0016" class="elsevierStylePara elsevierViewall">For each core of liver tissue with a length &#62;4 mm&#44; serial shortening by 2 mm was performed until reaching the 4-mm core length&#46; Accordingly&#44; we acquired the following core lengths&#58; 58 samples with a core length of 4 mm&#44; 51 samples with a core length of 6 mm&#44; 42 samples with a core length of 8 mm&#44; 23 samples with a core length of 10 mm&#44; and eight samples with a core length of 12 mm &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46;&#160;1</a>&#41;&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="cesectitle0010">Assessment of adequacy criteria</span><p id="para0017" class="elsevierStylePara elsevierViewall">An adequate sample is a liver tissue specimen that can express the different pathological criteria without difference from the larger samples&#46; To assess adequacy&#44; we considered the pathological criteria defined by the largest core size as the internal reference standard&#46; Determining the etiological diagnosis was out of the scope of this study in the determination of the adequacy criteria&#46; We relied on defining adequacy to determine the adequate core length and CPT number&#44; while width was that of the 16 G Tru-cut needle&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall">The current study design of serial shortening of samples to assess the adequacy criteria has been performed before in adults&#8217; studies by Colloredo et&#160;al&#46; <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a>&#46; In the present work&#44; we compared the pathological scores reported by the smallest available core length &#40;4 mm&#41; to those reported by the next largest core length &#40;6 mm&#41; to define the adequate core length&#46; Then&#44; we compared the 6-mm core length to the 8-mm core length to reach the largest available core length &#40;12 mm&#41;&#46; The smallest core length that could define the pathological scores with no significant difference from those reported by the larger core lengths was considered adequate&#46;</p><p id="para0019" class="elsevierStylePara elsevierViewall">The CPT numbers of the defined adequate core length were reported&#44; and the mean values were considered in the definition of the criteria of the adequate liver biopsy core&#46; However&#44; the width was standardized to the width of the liver biopsy cores obtained by the Tru-cut needle 16 G&#46; It was not feasible to obtain different widths for comparison&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="cesectitle0011">Histopathological evaluation</span><p id="para0020" class="elsevierStylePara elsevierViewall">For each liver section&#44; definite pathological parameters were recorded and summed into two items&#58; activity grade &#40;score&#58; 0-15&#41; and fibrosis stage &#40;score&#58; 0-4&#41;&#46; The activity grade included the following nine pathological items we reported previously <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&#58; &#40;1&#41; bile ductular proliferation&#44; &#40;2&#41; bile plugs&#44; &#40;3&#41; portal infiltrate with lymphocytes&#44; &#40;4&#41; neutrophils&#44; and &#40;5&#41; eosinophils&#44; &#40;6&#41; giant cell transformation of hepatocytes&#44; &#40;7&#41; hepatocyte swelling&#44; &#40;8&#41; rosette formation&#44; and &#40;9&#41; extramedullary hematopoiesis&#46; All reported items were given scores&#59; higher scores indicate a greater possibility of biliary atresia rather than nonbiliary atresia cholestasis <a class="elsevierStyleCrossRef" href="#bib0006">&#91;6&#93;</a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table&#160;1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0021" class="elsevierStylePara elsevierViewall">Liver fibrosis was classified into five stages <a class="elsevierStyleCrossRef" href="#bib0007">&#91;7&#93;</a>&#44; as reported in <a class="elsevierStyleCrossRef" href="#tbl0001">Table&#160;1</a>&#46; Two senior pathologists interpreted all histopathological findings&#46; All pathological criteria were assessed three times&#44; one month apart&#44; and median values were reported&#46; The intra- and interobserver kappa values for different pathological parameters were 0&#46;865&#8211;0&#46;932 and 0&#46;813&#8211;0&#46;842&#44; respectively&#46; For the histopathological findings that showed no concordance between the two pathologists&#44; a shared reassessment was performed&#46;</p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;5</span><span class="elsevierStyleSectionTitle" id="cesectitle0012">Statistical analysis</span><p id="para0022" class="elsevierStylePara elsevierViewall">Quantitative data are expressed as the mean &#177; standard deviation&#46; Kendall&#39;s coefficient of concordance was used to assess agreement among different core lengths&#46; It was done on two-by-two comparisons and didn&#39;t compare all biopsy lengths at the same time&#46; This test results in a number that varies from 0 &#40;complete disagreement&#41; to 1 &#40;complete agreement&#41; <a class="elsevierStyleCrossRef" href="#bib0008">&#91;8&#93;</a>&#46; We also performed one-way analysis of variance &#40;ANOVA&#41; to analyze differences in the means of the dependent variable &#40;score&#41; when stratified by the levels of the independent variable &#40;biopsy length&#41;&#46; The kappa coefficient was calculated to measure the intra- and interobserver agreements&#46; A P-value of &#60; 0&#46;05 was used to indicate statistically significant results&#46; SPSS 21&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41; was used to perform the statistical analysis&#46;<span class="elsevierStyleBold">Results</span></p></span></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="cesectitle0013">Adequate core length for the NC activity</span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0014">Adequacy criteria for the activity grade</span><p id="para0023" class="elsevierStylePara elsevierViewall">By serial comparison of the activity score reported by the 4-mm core length to that reported by the larger core length and so on&#44; it was found that the 4-mm core length was concordant with the 6-mm core length&#44; P&#160;&#61;&#160;0&#46;257 and W&#61;0&#46;988&#46; The 6-mm core length was concordant with the 8 mm core length&#44; P&#160;&#61;&#160;0&#46;180 and W&#61;0&#46;966&#46; The 8-mm core length was concordant with the 10-mm core length&#44; P&#160;&#61;&#160;1&#46;0 and W&#61;1&#46;0&#46; Finally&#44; the 10-mm core length was concordant with the 12-mm core length&#44; P&#160;&#61;&#160;1&#46;0 and W&#61;1&#46;0&#46; Therefore&#44; the adequate core length for reporting the total activity grade of NC was 4 mm &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46;&#160;2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2</span><span class="elsevierStyleSectionTitle" id="cesectitle0015">Adequacy criteria for individual parameters of NC activity</span><p id="para0024" class="elsevierStylePara elsevierViewall">By serial comparisons of different core lengths for every individual histopathological parameter of NC activity&#44; it was found that the 4-mm core length showed concordance with the larger core lengths &#40;P &#62; 0&#46;05 and W&#61;0&#46;966-1&#46;0&#44; for all&#41;&#46; Therefore&#44; the adequate core length for the individual parameters of NC activity was 4 mm&#46; <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46;&#160;3</a> summarizes the results of the comparison of different core lengths for every histopathological parameter&#46;</p><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="cesectitle0016">Adequate core length for the NC fibrosis stage</span><p id="para0025" class="elsevierStylePara elsevierViewall">Conversely&#44; serial comparison of core lengths to define the adequate length for fibrosis assessment showed no concordance between the 4-mm core length and the 6-mm core length &#40;P&#61;0&#46;014 and W&#61;0&#46;598&#41;&#46; In contrast&#44; there was concordance between serial core lengths of 6&#44; 8&#44; 10&#44; and 12 mm &#40;P&#62;0&#46;05 and W&#61;0&#46;99-1&#46;0&#44; for all&#41;&#46; Therefore&#44; the fibrosis stage assessment&#39;s adequate core length was 6 mm &#40;<a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46;s&#160;3</a> and <a class="elsevierStyleCrossRef" href="#fig0004">4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0004"></elsevierMultimedia></span><span id="sec0012a" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">5</span><span class="elsevierStyleSectionTitle" id="cesectitle0017">Adequate complete portal tract number for NC activity and fibrosis stage</span><p id="para0026" class="elsevierStylePara elsevierViewall">The 4-mm core lengths were found to have a CPT number of 8 &#177; 3&#46; Therefore&#44; the adequate CPT number for reporting activity grade ranged from 5 to 11 per core&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">The 6-mm core lengths were found to have a CPT number of 11 &#177; 3&#46; Therefore&#44; the adequate CPT numbers for reporting the fibrosis stage ranged from 8 to 14 per core&#46;</p></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">6</span><span class="elsevierStyleSectionTitle" id="cesectitle0018">ANOVA results</span><p id="para0028a" class="elsevierStylePara elsevierViewall">ANOVA of all examined histopathological parameters revealed comparable results to those of Kendall&#39;s coefficient of concordance&#46; Moreover&#44; Kendall&#39;s coefficient test had the benefit of considering the related-samples concordance and presenting the continuous field information&#44; as shown in <a class="elsevierStyleCrossRef" href="#fig0002">Figs&#46;&#160;2</a> and <a class="elsevierStyleCrossRef" href="#fig0004">4</a>&#46; P-values derived from the ANOVA of the studied parameters were as follows&#58; activity grade&#61;0&#46;17&#44; bile ductular proliferation&#61;0&#46;560&#44; bile plugs&#61;0&#46;810&#44; lymphocyte infiltrate&#61;0&#46;910&#44; neutrophil infiltrate&#61;0&#46;894&#44; eosinophil infiltrate&#61;0&#46;913&#44; giant cells&#61;0&#46;543&#44; hepatocyte swelling&#61;0&#46;506&#44; rosette formation&#61;0&#46;860&#44; extramedullary hematopoiesis&#61;0&#46;992&#44; and fibrosis stage&#61;0&#46;685&#46;</p></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">7</span><span class="elsevierStyleSectionTitle" id="cesectitle0019">Discussion</span><p id="para0029" class="elsevierStylePara elsevierViewall">Despite progress in investigational tools and innovative imaging techniques&#44; liver biopsy remains vital in diagnosing many pediatric liver disorders&#46; An adequate sample should be obtained to avoid misdiagnosis as a consequence of sampling errors&#46; The American Association for the Study of Liver Diseases recommended the importance of a sufficient sample size to correctly diagnose diffuse liver disorders <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a>&#46; Many studies in adults concluded that the smaller the liver sample was&#44; the less accurate the assessment of both the grade of activity and the stage of fibrosis of diffuse liver disorders <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0009">&#91;9&#93;</a>&#46;</p><p id="para0030" class="elsevierStylePara elsevierViewall">Optimal biopsy length is the subject of debate because an accurate diagnosis of some diseases can be made with short samples&#46; Studies in patients with viral hepatitis have shown that grading and staging accuracy is reduced in biopsies less than 2&#46;0 cm in length <a class="elsevierStyleCrossRef" href="#bib0009">&#91;9&#93;</a>&#46;</p><p id="para0031" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; no studies have evaluated Tru-cut needle liver biopsy adequacy criteria in infants with liver diseases&#46; Data from the adult literature recommend using a 16 G needle and a biopsy length of 2 to 3 cm to ensure adequate biopsy&#46; These defined adequacy criteria allow for more straightforward pathological evaluations with more significant numbers of CPTs visualized than the 18 G needle <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a>&#46;</p><p id="para0032" class="elsevierStylePara elsevierViewall">The present study revealed that a 4-mm core length is an adequate core length for NC activity grade assessment&#46; It has been shown that this core length gives the same histopathological scores for activity grade as those reported by the larger core lengths of 6&#44; 8&#44; 10&#44; and 12 mm &#40;the highest core length&#41;&#46; Moreover&#44; the adequate CPT number for assessing the NC activity grade was found to be 8&#177;3&#46;</p><p id="para0033" class="elsevierStylePara elsevierViewall">In the liver fibrosis assessment&#44; to determine the size of an adequate liver biopsy&#44; the variability of the liver fibrosis distribution within the liver for the particular disease must be known&#44; which is likely to change with the disease stage&#46; Adequate biopsy samples need to be considered in light of the degree to which small inadequate biopsies tend to underestimate both disease grade and stage <a class="elsevierStyleCrossRef" href="#bib0010">&#91;10&#93;</a>&#46;</p><p id="para0034" class="elsevierStylePara elsevierViewall">The present study revealed that the 6-mm core length is the adequate core length for reporting the fibrosis stage&#46; This core length showed concordance with the fibrosis stages reported by the larger core lengths of 8&#44; 10&#44; and 12 mm &#40;the highest core length&#41;&#46; Additionally&#44; the adequate CPT number for assessing the NC fibrosis stage was found to be 11 &#177;3&#46;</p><p id="para0035" class="elsevierStylePara elsevierViewall">The larger core length required for assessing the NC fibrosis stage than that needed for evaluating the NC activity grade follows the previous recommendation that adequate liver biopsy would be larger when there is a need to assess the stage of fibrosis&#46; Moreover&#44; if cirrhosis is suspected&#44; a cutting rather than a suction needle is recommended <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a>&#46;</p><p id="para0036" class="elsevierStylePara elsevierViewall">Colloredo et&#160;al&#46; <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a> evaluated the effects of core length and width on the grading and staging of diffuse liver pathology&#46; The methodology consisted of progressively reducing the original samples&#8217; length and width&#44; all at least 2&#46;5-3 cm long&#46; Their study provided evidence that both the length and the width of the biopsy core affect the grading and staging and that examining shorter and thinner samples leads to underestimating disease severity&#46; The result was that a 20-mm length is the &#8216;minimum&#8217; recommended size of a liver biopsy containing a number of CPTs &#8805;11 for the histological assessment of activity and fibrosis in chronic viral hepatitis in adults&#46;</p><p id="para0037" class="elsevierStylePara elsevierViewall">The American Association for the Study of Liver Diseases guidelines recommended that a biopsy of at least 2-3 cm in length&#44; 11 CPT&#44; and 16 G in caliber is recommended for the accurate diagnosis&#44; grading&#44; and staging of fibrosis in diffuse liver disorders in adults <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a>&#46;</p><p id="para0038" class="elsevierStylePara elsevierViewall">The use of liver biopsy guidelines in clinical practice from the Royal College of Pathology&#44; British Society of Gastroenterology&#44; and the Royal College of Radiologists recommended that a 16 G needle be used for the percutaneous approach&#46; However&#44; an 18 G needle should be used for percutaneous biopsy of a solid lesion&#44; and the length of the sample should be &#8805;20 mm <a class="elsevierStyleCrossRef" href="#bib0003">&#91;3&#93;</a>&#46;</p><p id="para0039" class="elsevierStylePara elsevierViewall">The Royal College of Pathologists published its first guidelines on liver biopsy in 2008 and updated its guidelines in 2014 to suggest minimum adequacy requirements for samples to be at least 10 mm long and to contain six portal tracts <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&#46; These guidelines have now been revised to ensure that all recommendations are up to date&#46; In the third set of guidelines published in 2020 state that if the liver biopsy is adequate&#44; it should be at least 20 mm in length obtained by a 16 G needle and contain at least ten CPTs&#46; A biopsy of less than 10 mm is of limited diagnostic value&#44; and a second pass should be considered&#46; If the biopsy core is between 10 and 20 mm in length&#44; the diagnosis may be compromised&#46; A second pass should be considered&#44; especially if the biopsy&#39;s main indications are staging fibrosis <a class="elsevierStyleCrossRef" href="#bib0012">&#91;12&#93;</a>&#46;</p><p id="para0040" class="elsevierStylePara elsevierViewall">Although adult studies have recommended a biopsy length of 20 mm&#44; the adequacy of a smaller sample size was apparent in the present study&#46; This difference could be attributed to some technical factors&#46; The ratio of the obtained sample to the relatively smaller infant liver approximates the ratio used in adults&#46; Moreover&#44; this difference could be due to the use of core-aspiration needles&#44; such as Menghini needles&#44; in some adult studies<a class="elsevierStyleCrossRef" href="#bib0003">&#91;3&#93;</a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a>&#44; which are less traumatizing and can allow for the acquisition of a longer core than the Tru-cut needle used in our study&#46; On the other hand&#44; Menghini needles were avoided&#44; in our study&#44; because the samples obtained tend to be more fragmented&#46; Some adult studies used more than one pass to acquire the target core length<a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013">&#91;13&#93;</a>&#46; We avoided multiple needle passes in the present study to decrease the biopsy-related complications associated with multiple passes <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a>&#46;</p><p id="para0041" class="elsevierStylePara elsevierViewall">Understanding the differences between the liver pathology in neonates and infants from those in adults explains the differences in liver specimen adequacy criteria between pediatric patients and adults&#46; Application of the adequacy criteria reported in adults would miss the diagnosis in many neonates and infants who could be accurately diagnosed with smaller specimens than those defined from adult studies&#46;</p><p id="para0042" class="elsevierStylePara elsevierViewall">A limitation of this study is the retrospective nature&#44; which could not permit a comparison between different needle sizes&#58; 16 G vs&#46; 18 G&#46; Meanwhile&#44; it was challenging to acquire different widths from the studied cores in the present study&#46; However&#44; in our center&#44; we routinely use Tru-cut needles 16 G because our former 18 G needles yielded fragmented tissue samples with fewer CPT numbers&#46; Palmer et&#160;al&#46; <a class="elsevierStyleCrossRef" href="#bib0013">&#91;13&#93;</a> reported that specimen adequacy was not significantly affected by the biopsy gauge of 16 G vs&#46; 18 G&#46; However&#44; other studies reported that 16 G needles yielded better quality samples with a higher CPT number than 18 G needles &#91;<a class="elsevierStyleCrossRef" href="#bib0013">13</a>&#44; <a class="elsevierStyleCrossRef" href="#bib0014">14</a>&#93;&#46;</p><p id="para0043" class="elsevierStylePara elsevierViewall">In conclusion&#44; to the best of our knowledge&#44; the present work is the first to assess liver biopsy sample adequacy criteria for the accurate assessment of neonatal liver disorders&#44; namely&#44; NC&#46; A liver specimen acquired with a 16 G Tru-cut needle with a 4-mm length and a CPT of 5-11 is accurate for activity grading&#46; However&#44; to stage fibrosis for NC&#44; a 16 G Tru-cut needle sample should be at least 6 mm in length with CPT numbers of 8-14&#46;</p></span><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021">Financial support</span><p id="para0045" class="elsevierStylePara elsevierViewall">This study was funded by the National Liver Institute&#44; Menoufia University&#44; Egypt&#46; The funders had no particular role in the study design&#44; recruitment of individuals&#44; data analysis&#44; or writing of the report&#46;</p></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019a">Author contributions</span><p id="para0028" class="elsevierStylePara elsevierViewall">Behairy BE&#44; Allam AA&#44; Hegazy SG&#44; Taie DM&#44; and Sira AM were involved in the study concept and design&#59; Behairy BE&#44; Allam AA&#44; Hegazy SG&#44; and Sira AM were involved in the recruitment of patients&#44; clinical management and follow-up and data acquisition&#59; Taie DM performed the histopathological examination&#59; Sira A performed the statistical analysis and designed the figures&#59; Behairy BE&#44; Allam AA&#44; and Sira AM performed data interpretation&#59; Behairy BE&#44; Allam AA&#44; Taie DM&#44; and Sira AM wrote the manuscript&#59; all the authors reviewed the manuscript and ultimately approved it for submission&#46;</p></span></span>"
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          "titulo" => "Materials and methods"
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              "titulo" => "Liver biopsy sampling and processing"
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          "titulo" => "Adequate core length for the NC activity"
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              "titulo" => "Adequacy criteria for individual parameters of NC activity"
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          "titulo" => "Adequate core length for the NC fibrosis stage"
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          "identificador" => "sec0016"
          "titulo" => "Financial support"
        ]
        12 => array:2 [
          "identificador" => "sec0012"
          "titulo" => "Author contributions"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-01-29"
    "fechaAceptado" => "2021-03-03"
    "PalabrasClave" => array:1 [
      "en" => array:2 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1549127"
          "palabras" => array:5 [
            0 => "Adequacy criteria"
            1 => "Infants"
            2 => "Liver biopsy"
            3 => "Neonatal cholestasis"
            4 => "Tru-cut needle"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1549126"
          "palabras" => array:4 [
            0 => "CPT"
            1 => "CPTs"
            2 => "G"
            3 => "NC"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "highlights" => array:2 [
      "titulo" => "Highlights"
      "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><p id="spara006" class="elsevierStyleSimplePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">&#8226;</span><p id="para0001" class="elsevierStylePara elsevierViewall">Liver biopsy remains a cornerstone in the assessment of diffuse liver diseases&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">&#8226;</span><p id="para0002" class="elsevierStylePara elsevierViewall">Defining adequacy criteria for liver specimens avoids the impact of sampling errors&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">&#8226;</span><p id="para0003" class="elsevierStylePara elsevierViewall">Many studies have defined adequacy criteria of adult liver biopsy&#59; however&#44; it is the first study that assesses the adequacy criteria in neonatal cholestasis &#40;NC&#41;&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0004"><span class="elsevierStyleLabel">&#8226;</span><p id="para0004" class="elsevierStylePara elsevierViewall">A core length of 4 mm with a complete portal tract number &#40;CPT&#41; of 8&#177;3 is considered adequate for NC activity assessment&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0005"><span class="elsevierStyleLabel">&#8226;</span><p id="para0005" class="elsevierStylePara elsevierViewall">A core length of 6 mm with a CPT number of 11&#177;3 is required to assess the fibrosis stage adequately in NC&#46;</p></li></ul></p></span>"
    ]
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0002" class="elsevierStyleSection elsevierViewall"><p id="spara007" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Introduction and Objectives&#58;</span> Assessment of liver biopsy sample adequacy criteria is essential to avoid sampling errors in patients with diffuse liver pathology&#46; Many studies have evaluated these criteria in adults&#59; however&#44; no previous studies have been performed on neonatal liver disorders&#46; We aimed to assess the adequacy criteria of Tru-cut needle liver biopsy samples in infants with neonatal cholestasis &#40;NC&#41;&#46; <span class="elsevierStyleItalic">Methods&#58;</span> In a retrospective analysis of infants who underwent liver biopsy for NC within a one-year duration&#44; 58 specimens were recruited&#46; The core lengths after fixation were measured&#46; All samples were acquired with a 16-gauge &#40;G&#41; Tru-cut needle&#46; Serial shortening of these samples was performed to define the smallest core length that gives representative parenchyma that could determine the activity grade and fibrosis stage reported by larger cores&#46; <span class="elsevierStyleItalic">Results&#58;</span> It was found that a 4-mm core length with a complete portal tract &#40;CPT&#41; number of 8&#177;3 could adequately assess the NC activity grade&#46; In addition&#44; a 6-mm core length with a CPT number of 11&#177;3 could adequately estimate NC fibrosis stage&#46; <span class="elsevierStyleItalic">Conclusions&#58;</span> The adequacy criteria of liver tissue samples for the accurate assessment of NC are different from those defined for adult diffuse liver pathology&#46; At least a 4-mm core length with a CPT number of 8&#177;3 and a 6-mm core length with a CPT number of 11&#177;3 acquired by a 16-G Tru-cut needle should be used to assess NC activity grade and fibrosis stage&#44; respectively&#46;</p></span>"
      ]
    ]
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Flow chart of the included and excluded cases and the core lengths of the included specimens before and after serial shortening&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Kendall&#39;s coefficient of concordance for the assessment of the adequate core length for the activity grade&#46; A&#41; Comparison between the activity reported by the core lengths of 4 and 6 mm&#44; P&#61;0&#46;257&#46; The upper diagram represents the activity scores reported for every core length&#46; The lower diagram represents the ranked means and frequencies for every core length&#46; B&#41; Comparison between core lengths of 6 and 8 mm&#44; P&#61;0&#46;180&#59; C&#41; Comparison between core lengths of 8 and 10 mm&#44; P&#61;1&#46;0&#59; D&#41; Comparison between core lengths of 10 and 12 mm&#44; P&#61;1&#46;0&#46;</p>"
        ]
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          0 => array:3 [
            "identificador" => "alt0003"
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        "descripcion" => array:1 [
          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Summary diagram for comparing different core lengths for every pathological item assessed together with the activity grade and fibrosis stage&#46; For example&#44; the box summarizing the fibrosis stage assessment results showed that the 4-mm core length reported a fibrosis stage lower than that reported by the 6-mm core length&#46; However&#44; the fibrosis stages reported by the core lengths of 6&#44; 8&#44; 10&#44; and 12 mm showed no significant differences among them&#46; Therefore&#44; the adequate core length for reporting the fibrosis stage was 6 mm&#46;</p>"
        ]
      ]
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        "etiqueta" => "Fig&#46; 4"
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            "rol" => "short"
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          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Kendall&#39;s coefficient of concordance for the assessment of the adequate core length for the fibrosis stage&#46; A&#41; Comparison between the fibrosis stages reported by core lengths of 4 and 6 mm&#44; P&#61;0&#46;014&#46; The upper diagram represents the fibrosis stage reported for every core length&#46; The lower diagram represents the ranked mean and frequency for every core length&#46; B&#41; Comparison between core lengths of 6 and 8 mm&#44; P&#61;1&#46;0&#46; C&#41; Comparison between core lengths of 8 and 10 mm&#44; P&#61;0&#46;317&#46; D&#41; Comparison between the core lengths of 10 and 12 mm&#44; P&#61;1&#46;0&#46;</p>"
        ]
      ]
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        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Histological findings and their grades&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0003"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Bile ductular proliferationNone&#58; Average number of bile ductules per portal tract &#60; 5Mild&#58; Average number of bile ductules per portal tract between 5 to 9Moderate&#58; Average number of bile ductules per portal tract &#8805; 10Marked&#58; Elongated&#44; attenuated&#44; angulated bile ductules in addition to proliferation &#40;average number of bile ductules per portal tract &#8805; 10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0004"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0123&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0005"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Bile plug in portal ductulesAbsentPresent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0007"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Lymphocytic infiltrate in portal regionNone &#40;presence of lymphocytes up to 4 cells in the portal tract&#59; normal resident lymphocytes&#41;Mild &#40;presence of large number of lymphocytes in the portal tract without presence of lymphoid aggregates&#41;Moderate&#8211;marked &#40;presence of large number of lymphocytes in the portal tract with presence of lymphoid aggregates&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Neutrophilic infiltrate in portal regionAbsent or mild &#40;presence of few numbers around some bile ducts&#41;Moderate-marked &#40;presence of large numbers around some bile ducts&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0011"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Eosinophilic infiltrate in portal regionAbsent or mild &#40;presence of few numbers around some bile ducts&#41;Moderate-marked &#40;presence of large numbers around some bile ducts&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Multinucleated hepatocytes &#40;giant cells&#41;NoneAround central veinDiffuse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Hepatocellular swellingNoneMild&#47;focalPeriportal&#47;diffuse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Rosette formationAbsentPresent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0019"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Extramedullary hematopoiesisAbsentPresent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Total NC activity score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0023"></a><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Grades of fibrosisGrade 0&#58; absent or fibrous expansion of some portal areasGrade 1&#58; fibrous expansion of most portal areasGrade 2&#58; focal porto-portal bridgingGrade 3&#58; marked bridgingGrade 4&#58; cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">01234&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Total fibrosis stage score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "descripcion" => array:1 [
          "en" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">Neonatal cholestasis histopathological activity score and fibrosis stage</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec1"
          "bibliografiaReferencia" => array:14 [
            0 => array:3 [
              "identificador" => "bib0001"
              "etiqueta" => "&#91;1&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                  ]
                  "host" => array:1 [
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            ]
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              "etiqueta" => "&#91;2&#93;"
              "referencia" => array:1 [
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                  ]
                  "host" => array:1 [
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            ]
            2 => array:3 [
              "identificador" => "bib0003"
              "etiqueta" => "&#91;3&#93;"
              "referencia" => array:1 [
                0 => array:2 [
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                      "titulo" => "Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology&#44; the Royal College of Radiologists and the Royal College of Pathology"
                      "autores" => array:1 [
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                          "etal" => true
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                            0 => "J Neuberger"
                            1 => "J Patel"
                            2 => "H Caldwell"
                            3 => "S Davies"
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                  "host" => array:1 [
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                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0004"
              "etiqueta" => "&#91;4&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of liver biopsy size on histological evaluation of chronic viral hepatitis&#58; the smaller the sample&#44; the milder the disease"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G Colloredo"
                            1 => "M Guido"
                            2 => "A Sonzogni"
                            3 => "G&#46; Leandro"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
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                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
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Article information

ISSN: 16652681
Original language: English

DOI:10.1016/j.aohep.2021.100548

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Year/Month	Html	Pdf	Total

2024 November	4	2	6
2024 October	43	10	53
2024 September	71	14	85
2024 August	54	13	67
2024 July	44	4	48
2024 June	27	12	39
2024 May	42	9	51
2024 April	48	14	62
2024 March	47	13	60
2024 February	63	5	68
2024 January	74	3	77
2023 December	51	10	61
2023 November	51	7	58
2023 October	74	9	83
2023 September	49	2	51
2023 August	52	5	57
2023 July	59	6	65
2023 June	56	6	62
2023 May	107	9	116
2023 April	44	0	44
2023 March	49	4	53
2023 February	43	7	50
2023 January	39	6	45
2022 December	30	6	36
2022 November	36	12	48
2022 October	21	5	26
2022 September	25	6	31
2022 August	17	8	25
2022 July	13	8	21
2022 June	14	11	25
2022 May	15	7	22
2022 April	21	13	34
2022 March	14	11	25
2022 February	27	8	35
2022 January	68	9	77
2021 December	39	23	62
2021 November	23	18	41
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