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Advanced fibrosis more likely in children with zone 1 hepatic steatosis

Data from a study on pediatric nonalcoholic fatty liver disease and nonalcoholic steatohepatitis showed that children with zone 1 steatosis were more likely to have advanced fibrosis and children with zone 3 steatosis were more likely to have steatohepatitis.

“The histologic triad of classically described NASH in adults includes fat accumulation in hepatocytes, inflammation, and liver injury as manifest by hepatocyte ballooning,” Jonathan A. Africa, MD, from the University of California, San Diego School of Medicine, and colleagues wrote. “These same features can be identified in the livers of children with NAFLD, but there are distinct differences in the microscopic appearance in many pediatric cases.”

According to Africa and colleagues, the accumulation in hepatocytes can be subdivided as panacinar (even distribution), zone 1 (periportal), zone 3 (centrilobular or pericentral) and azonal (uneven distribution). While adults with NAFLD typically have inflammation and fibrosis in zone 3 and not zone 1, children have previously presented in both zones.

The study comprised 776 pediatric patients enrolled from the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with biopsy-confirmed steatosis in zone 1 (n = 146) or zone 3 (n = 244) or had azonal (n = 59) or panacinar distribution (n = 327).

Patients with zone 3 steatosis were older (14.7 vs 10.8 years; P < .001), taller (167.6 vs. 149.9 cm; P < .001) and heavier (97.7 vs. 67.9 kg; P < .001) than patients with zone 1, and had higher BMI (34.5 vs. 29.6 kg/m²; P <.001) higher triglycerides (164 vs. 125 mg/dL; P < .001) and higher insulin (39 vs. 25 µU/mL; P < .001). Patients with zone 1 were more likely to be Hispanic (75% vs. 57.6%; P = .001).

Additionally, biopsies with zone 3 steatosis showed more ballooning (48% vs 29%; P < .001), higher NAFLD Activity Score (4.1 vs 3.7; P = .014), a greater frequency definite NASH (30% vs 6%; P < .001) and less portal inflammation (75% vs. 97%; P < .001) compared with zone 1 steatosis.

Multivariate analysis showed that children with zone 1 steatosis had a significantly higher risk for advanced fibrosis than children with zone 3 steatosis (OR = 2.34; 95% CI, 1.03-5.52). Children younger than 13 years had a higher risk for zone 1 steatosis compared with older children (OR = 6.3; 95% CI, 3.9-10.4), whereas those aged 13 years or older were more likely to have zone 3 steatosis (OR = 9; 95% CI, 6.3-13.2). Additionally, girls were more likely to have zone 3 steatosis compared with boys (OR = 1.6; 95% CI, 1.1-2.3).

“Zone 1 and zone 3 steatosis are two distinct subphenotypes of pediatric NAFLD that may be informative of risk differences in the progression of NAFLD, namely in terms of advanced fibrosis and steatohepatitis, respectively,” the researchers wrote. “A better understanding of the pathophysiologic differences between these steatosis zonality patterns may provide opportunities for targeted personalized therapies for children with NAFLD in the future.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.