Association between puberty and features of nonalcoholic fatty liver disease

Abstract

Background & aims: Physiological changes that occur during puberty might affect pathologic features of nonalcoholic fatty liver disease (NAFLD). We investigated associations between pubertal development and clinical and histopathologic features of NAFLD.

Methods: We studied 186 children (age <18 years, 143 boys) with biopsy-proven NAFLD. The population was divided into 3 groups on the basis of Tanner stage (prepuberty, puberty, and postpuberty). Clinical characteristics and histologic features were compared among groups. Multivariable regression models were used to adjust for potential confounders.

Results: After adjusting for other factors, hyperuricemia and low levels of high-density-lipoprotein cholesterol were more prevalent among children who entered puberty with lower levels of quantitative insulin sensitivity check index (P < .05). The degree of steatosis, numbers of Mallory-Denk bodies, and diagnostic categories of NAFLD differed among groups (P < .05). There were potential sex differences in associations between stages of puberty and lobular inflammation, hepatocyte ballooning, and borderline steatohepatitis of zone 3; these were therefore not included in multivariable analyses of the overall population. After adjustment for different sets of confounders, patients at or beyond puberty were less likely to have high-grade steatosis, severe portal inflammation, borderline steatohepatitis (zone 1), or a high stage of fibrosis than patients who had not entered puberty (P < .05). On the contrary, the prevalence of Mallory-Denk body was greater among postpuberty subjects (P = .06).

Conclusions: Steatosis, portal inflammation, and fibrosis are less severe during or after puberty than before puberty among subjects with NAFLD. Postpubescent individuals have a lower prevalence of borderline steatohepatitis of zone 1 but are more likely to have Mallory-Denk bodies. These findings indicate that puberty affects the pathologic features of NAFLD.

Figure 1. Associations of Pubertal Development with Steatosis, Steatohepatitis, Mallory-Denk bodies, and Portal Inflammation in Total Population

Figures show the associations of pubertal stages (horizontal axis) with the prevalence of up to mild (grade 0–1), moderate (grade 2) and severe (grade 3) steatosis (left upper), the prevalence of none (simple steatosis), borderline steatohepatitis zone 3 (or adult pattern), borderline steatohepatitis zone 1(pediatric pattern), and definite steatohepatitis (right upper), the prevalence of severe (grade 2) portal inflammation (left lower), and the prevalence of Mallory-Denk bodies (right lower). P-values are from exact tests. SH: steatohepatitis