Liver Biopsy in Children

Dezsőfi, Antal; Baumann, Ulrich; Dhawan, Anil; Durmaz, Özlem; Fischler, Björn; Hadžić, Nedim; Hierro, Loreto; Lacaille, Florence; Mclin, Valérie Anne; Nobili, Valério; Socha, Piotr; Vajro, Pietro; Knisely, Alexander S.

doi:10.1097/mpg.0000000000000632

Cited by 179 publications

(81 citation statements)

References 138 publications

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“…In 2012 the ESPGHAN panel[ 36 ] indicated that although a liver biopsy is required for a definitive NAFLD diagnosis, its invasive nature and high cost prohibit the use of biopsies as a screening procedure. The same panel recently[ 53 ] highlighted that indications for liver biopsy in NAFLD are still controversial and there is limited available evidence for the formulation of guidelines. Indications for liver biopsy are only based on expert opinions that must take into consideration a differential diagnosis and the risk of progression of liver disease to cirrhosis.…”

Section: Liver Biopsy Histologymentioning

confidence: 99%

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

Clemente

Mandato

Poeta

et al. 2016

WJG

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168

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Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.

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Section: Liver Biopsy Histologymentioning

confidence: 99%

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

Clemente

Mandato

Poeta

et al. 2016

WJG

Self Cite

168

160

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“…Liver biopsy has been considered a standard method for evaluating liver fibrosis and steatosis in children with chronic hepatitis C (CHC) [1–3]. However, it has several limitations: it is invasive and painful, has inter- and intraobserver variability, and is prone to sampling errors [1, 3].…”

Section: Introductionmentioning

confidence: 99%

“…However, it has several limitations: it is invasive and painful, has inter- and intraobserver variability, and is prone to sampling errors [1, 3]. Therefore, efforts have been made to develop alternative, noninvasive methods to liver biopsy, including imaging studies (elastography) and serum biomarkers [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

et al. 2017

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BackgroundThere is a need for validation of noninvasive alternatives to liver biopsy for the evaluation of fibrosis in children with chronic hepatitis C (CHC). The aim of this study was to evaluate the diagnostic performance of serum biomarkers modified by the body mass index z-score (BMI z-score) for the detection of fibrosis and steatosis in children with CHC.MethodsThirty children aged 9.4 ± 3.7 years (14 males, 16 females) with CHC underwent liver biopsy. Fibrosis was scored using a 5-point METAVIR scale (≥2 = significant fibrosis). For all the children, the following noninvasive markers were calculated: The aspartate transaminase (AST)-to-platelets ratio index (APRI), the modified APRI (M-APRI: BMI z-score × APRI), the Fibrosis-4 index (FIB-4), the modified FIB-4 (M-FIB-4: BMI z-score × FIB-4), and a novel marker, B-AST (BMI z-score × AST). The area under the receiver operator characteristic curve (AUROC) was calculated to detect significant fibrosis and steatosis.ResultsIn the histopathological evaluation, 22/30 (73%) patients presented with fibrosis, and 8/30 (27%) presented with steatosis. For the detection of significant fibrosis, the AUROCs for M-APRI, M-FIB-4 and B-AST were 0.842, 0.823, and 0.848, respectively. For significant steatosis, the AUROCs were more than 0.9 for all markers that included the BMI z-score. B-AST, with a cut-off of 92.8, showed 71% sensitivity and 95% specificity for detecting significant fibrosis. For predicting severe steatosis, B-AST had 100% sensitivity and 92% specificity. Negative values of all three markers that included BMI z-scores excluded all patients with both significant fibrosis and significant steatosis.ConclusionsIncluding the BMI z-score in serum biomarker formulas enhances their diagnostic ability to detect significant fibrosis and steatosis. B-AST may thus act as an effective alternative to liver biopsy.

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“…A percutaneous liver biopsy will be performed under sonographic control and in analgosedation, according to recommendations of the ESPGHAN Hepatology Committee [43] and local standards. Additionally, we will perform protocol liver biopsies routinely every 5 years after LT. Liver tissue will be processed for immunohistochemistry (hematoxylin and eosin staining; staining for CD3, CD4, and CD20).…”

Section: Methods and Designmentioning

confidence: 99%

Safety and Tolerance of Donor-Derived Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation: The MYSTEP1 Study

Hartleif

Schumm

Döring

et al. 2017

Stem Cells International

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Background Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT. Methods/Design 7 to 10 children undergoing living-donor pLT will be included in this open-label, prospective pilot trial. A dose of 1 × 106 MSCs/kg body weight will be given at two time points: first by intraportal infusion intraoperatively and second by intravenous infusion on postoperative day 2. In addition, participants will receive standard immunosuppressive treatment. Our primary objective is to assess the safety of intraportal and intravenous MSC infusion in pLT recipients. Our secondary objective is to evaluate efficacy of MSC treatment as measured by the individual need for immunosuppression and the incidence of biopsy-proven acute rejection. We will perform detailed immune monitoring to investigate immunomodulatory effects. Discussion Our study will provide information on the safety of donor-derived MSCs in pediatric living-donor liver transplantation and their effect on immunomodulation and graft survival.

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Liver Biopsy in Children

Cited by 179 publications

References 138 publications

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

Novel serum biomarkers modified by the body mass index z-score for the detection of liver fibrosis and steatosis in children with chronic hepatitis C

Safety and Tolerance of Donor-Derived Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation: The MYSTEP1 Study

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