Based on current recommendations, additional diagnostic evaluation should be initiated if a child has clinical symptoms of liver disease or if ALT is >80. Sex-specific reference ranges of ALT should be used in determining elevation of ALT. Pediatric NAFLD should be suspected for any child 9 years or older with obesity or if overweight with risk factors for NAFLD. Overall, the diagnosis of NAFLD in children remains a challenge. 25 Noninvasive biomarkers, such as the enhanced liver fibrosis score, and scoring systems, such as the Fibrosis-4 index, have been developed to trend fibrosis in NAFLD, but these are not currently validated in children. However, there are limitations of using ultrasound to quantify steatosis because although ultrasound has a reported sensitivity of 79.7% and specificity of 86.2% in the detection of hepatic steatosis for moderate-to-severe steatosis, 21 ultrasound is not sensitive in children with a low percentage of steatosis (9 kPa is associated with advanced histological fibrosis. Ultrasound is an inexpensive modality to detect hepatic steatosis. This histological progression of liver disease is associated with loss of glucose homeostasis, worsening obesity, and an increasing ALT. 19 Progression of liver disease occurs in up to one-third of children with NAFLD undergoing dietary and lifestyle modification, and it is marked by advancement of steatosis or fibrosis. Resolution of NASH has been observed in up to 28% of children, with 40% of children having improved fibrosis or steatosis.
The natural history of NAFLD in children undergoing dietary and lifestyle counseling is variable. Mild hepatic steatosis with zone 3 distribution with lobular inflammation, hepatocyte ballooning, and perisinusoidal fibrosis. Hematoxylin and eosin stain, original magnification 10×. By contrast, NAFLD histology in adults is typically characterized by zone 3 centered ballooning injury, inflammation, steatosis, and perisinusoidal fibrosis (Fig. This pattern has been termed zone 1 borderline pattern (Fig. When bridging fibrosis develops, the bridges connect the portal areas, leaving the central veins alone. Fibrosis begins around the portal areas, with hepatocyte trapping by collagen and extension of short septations into the surrounding parenchyma. Ballooned hepatocytes are mostly absent and, if present, are the same size as nonballooned cells. Mild lobular and portal inflammation is present. This pattern is characterized by steatosis that is most prominent in zone 1, forming around the portal areas. Pediatric NAFLD and NASH histology has been found to have distinct features not seen in adults with the disease. Fibrosis in NAFLD is assessed separately and staged using a semiquantitative scale of 0 to 4. The majority of patients with NASH have an NAS score ≥5. The NAS uses a semiquantitative scale to assess steatosis (0-3 score), lobular inflammation (0-3 score), and hepatocyte ballooning (0-2 score). The NAS was designed as a research tool and is not intended to confirm a clinical diagnosis. The NAFLD Activity Score (NAS) is a commonly used tool to assess liver involvement in NAFLD. A major limitation of liver biopsy is sampling variability due to lack of uniformity in liver disease involvement in NAFLD, and recommendations are for a liver biopsy length of >2 cm to ensure an adequate sample. The role of liver biopsy in NAFLD is to exclude other causes of chronic liver disease while also allowing for assessment of severity of steatosis, steatotic hepatitis, and degree of fibrosis. 1, 2, 14, 15 The decision to pursue a liver biopsy in a child with suspected NAFLD should be based on clinical judgment and discussion with the patient and family.
Most guidelines recommend a liver biopsy if the diagnosis is unclear, if there is concern for multiple diagnoses, or if there is persistent elevation of ALT despite lifestyle modifications. Liver biopsy is considered safe in children with a complication rate from percutaneous liver biopsy between 1% and 4%. However, the decision to perform a liver biopsy in NAFLD is a challenge because it is an invasive procedure. Liver biopsy remains the gold standard for the diagnosis of NAFLD. 1 An algorithm for initiation of further evaluation in children with NAFLD is proposed in Fig. ALT is the recommended initial screening test for NAFLD, and interpretation should be based on sex-specific reference ranges (normal ALT 80 U/L (41% compared with 21% in children with ALT 80 U/L. Screening for NAFLD is recommended for all obese children 9 years or older as defined by a BMI above the 95th percentile, and should also be considered for overweight children with a family history of NAFLD or the presence of risk factors.
0 kommentar(er)
