Liver biopsy in modern clinical practice: a pediatric point-of-view

Abstract

Liver biopsy remains the foundation of evaluation and management of liver disease in children, although the role of the liver biopsy is changing with development of alternative methods of diagnosis and advancement of hepatic imaging techniques. The indications for liver biopsy are evolving as current knowledge of etiologies, noninvasive biomarker alternatives, and treatment options in pediatric liver disease are expanding. The procedure can often be complicated in children by technical difficulties, cost, and smaller specimen size. Communication and partnership of clinicians with pathologists experienced in pediatric liver diseases are essential. DNA sequencing, novel imaging modalities, noninvasive biomarkers of fibrosis and apoptosis, proteomics, and genome-wide association studies offer potential alternative methods for evaluation of liver disease in children. This review presents specific indications, considerations, methods, complications, contraindications, and alternatives for pediatric liver biopsy.

Figure 1

In this case of biliary atresia (A–B) there is marked expansion of portal tracts by fibrosis as well as portal edema and prominent ductular reaction (part B), highlighted by cytokeratin 7 immunohistochemistry (B, inset). In cases of idiopathic neonatal hepatitis (C), portal fibrosis is less conspicuous and ductular reaction, if present, is inconspicuous. Lobular changes, including giant cell transformation (C, inset) are pronounced in this example. Alagille’s syndrome is characterized by prominent bile duct loss. A portal tract containing a hepatic artery but no accompanying bile duct is shown here (D). A, hematoxylin and eosin (H&E) (superior core) and Masson’s trichrome (inferior core), 20x. B, Masson’s trichrome, 100×; C–D, H&E, 40–100×.

Figure 2

Type I glycogen storage disease showing diffuse deposition of glycogen material within hepatocytes (A). Presence of glycogen is further supported by positive Periodic Acid Schiff (PAS) (B) and negative PAS-diastase staining (C).

Figure 3

In typical cases of early-stage NASH (adult pattern), portal tracts are usually normal (A–B) and centrilobular/perivenular sinusoidal fibrosis is present (C). Hepatocyte ballooning and Mallory bodies are characteristic features (the latter may be highlighted by ubiquitin immunohistochemistry, C-inset). In contrast, type II (pediatric pattern) NASH is characterized by portal-based fibrosis, often associated with portal inflammation (D–E), while central veins are spared (F). A and D, hematoxylin and eosin stain; B, C, E, and F, trichrome stain (original magnification 100–200×).