Original article
Liver, pancreas, and biliary tract
Association Between Puberty and Features of Nonalcoholic Fatty Liver Disease

https://doi.org/10.1016/j.cgh.2012.01.020Get rights and content

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.

Section snippets

Study Design and Population

We performed a cross-sectional analysis by using data from the NASH CRN Database study and the Treatment of NAFLD in Children (TONIC) clinical trial. The study design and data collected from the NAFLD Database study and TONIC trial have been reported recently.15, 16 Our study population required the following criteria: (1) age at enrollment was <18 years, (2) the presence of liver histologic data, (3) no chronic liver diseases other than NAFLD as assessed by serologies and/or histology, and (4)

Clinical Characteristics

A total of 186 children (age <18 years) with NAFLD were analyzed. Median and interquartile range (in months) of difference between the time of liver biopsy and the time of the clinical data collection were 2 (1, 2). Clinical characteristics of the patients were significantly different among the 3 pubertal stages (Table 2). As anticipated, pubertal development increased along with growth, age, and all the anthropometric measures; the associations were statistically significant, except for

Discussion

We conducted a cross-sectional analysis by using the largest prospective pediatric NAFLD database and found that pubertal stages were associated with regional anthropometric measures, clinical features of insulin resistance, and the severity of several histologic features of NAFLD. Pubertal stages were univariately associated with the severity of steatosis, portal inflammation (borderline), Mallory–Denk bodies, and the diagnostic categories of steatohepatitis in the overall population. Children

Acknowledgments

Members of the Nonalcoholic Steatohepatitis Clinical Research Network, Pediatric Clinical Centers, are listed in the Appendix.

The authors thank Dr Yuliya Lokhnygina, Department of Biostatistics, Duke University, Durham, NC, for her critical consideration and insight regarding statistical approach used in this analysis and her assistance in statistical analysis.

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    Conflicts of Interest The authors disclose no conflicts.

    Funding This publication was made possible by grant number UL1RR024128 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

    The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713) and the National Institute of Child Health and Human Development (NICHD). Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards in conduct of NASH CRN Studies (grants UL1RR024989, M01RR000750, M01RR00188, UL1RR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359). Dr Manal Abdelmalek is supported by an NIH/NIDDK K23 Career Development award (K23-DK062116).

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