Volume 58, Issue 5 pp. 632-636
Original Article: Hepatologyand Nutrition

A 4-Polymorphism Risk Score Predicts Steatohepatitis in Children With Nonalcoholic Fatty Liver Disease

Valerio Nobili

Corresponding Author

Valerio Nobili

Liver Research Unit, Bambino Gesù Children's Hospital and Research Institute, Roma

Address correspondence and reprint requests to Dr Valerio Nobili, Liver Research Unit, Bambino Gesù Children's Hospital and Research Institute, Square S. Onofrio 4, 00165 Rome, Italy (e-mail: [email protected]).Search for more papers by this author
Benedetta Donati

Benedetta Donati

Department of Pathophysiology and Transplantation, section Internal Medicine, Universita’ degli Studi di Milano, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Milan

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Nadia Panera

Nadia Panera

Liver Research Unit, Bambino Gesù Children's Hospital and Research Institute, Roma

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Apirom Vongsakulyanon

Apirom Vongsakulyanon

Department of Pathophysiology and Transplantation, section Internal Medicine, Universita’ degli Studi di Milano, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Milan

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Anna Alisi

Anna Alisi

Liver Research Unit, Bambino Gesù Children's Hospital and Research Institute, Roma

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Bruno Dallapiccola

Bruno Dallapiccola

Scientific direction, Bambino Gesù Children's Hospital and Research Institute, Roma, Italy

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Luca Valenti

Luca Valenti

Department of Pathophysiology and Transplantation, section Internal Medicine, Universita’ degli Studi di Milano, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Milan

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First published: 01 May 2014
Citations: 63

Drs Nobili and Donati participated equally in this study.

The authors report no conflicts of interest.

ABSTRACT

Objective:

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in industrialized countries in adults and children, following the trail of the epidemic diffusion of obesity. Nonalcoholic steatohepatitis (NASH) is a potentially serious form of NAFLD linked with a significant increase in overall and liver-related morbidity and mortality. Because diagnosis still requires liver biopsy, there is urgent need of developing noninvasive early markers. The aim of the present study was to assess whether the simultaneous detection of genetic risk factors could predict NASH.

Method:

We enrolled 152 untreated, consecutive obese children and adolescents with biopsy-proven NAFLD and increased liver enzymes. The PNPLA3 rs738409 C>G (I148 M), SOD2 rs4880 C>T, KLF6 rs3750861 G>A, and LPIN1 rs13412852 C>T polymorphisms were detected by Taqman assays.

Results:

A multivariate logistic model based on the genetic risk factors significantly predicted NASH (area under the receiver-operating characteristic curve [AUC] 0.75, 95% confidence interval [CI] 0.67–0.82, P < 0.0001), performing better than a clinical risk score identified at stepwise regression based on age, aspartate aminotransferase levels, and diastolic blood pressure (AUC 0.66, 95% CI 0.57–0.75). A single cutoff value of the genetic risk score had 90% sensitivity and 36% specificity for NASH. A risk score combining the clinical and genetic risk factors resulted in an AUC of 0.80 (95% CI 0.73–0.87).

Conclusions:

A score based on genetic risk factors significantly predicts NASH in obese children with increased liver enzymes, representing a proof-of-principle that genetic scores may be useful to predict long-term outcomes of the disease and guide clinical management.

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