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      A Systematic Review of NAFLD-Associated Extrahepatic Disorders in Youths

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          Abstract

          Background: There is growing evidence that non-alcoholic fatty liver disease (NAFLD) is a disease affecting not only the liver but also extrahepatic organs. Aim: To investigate whether in youths NAFLD is associated with extrahepatic complications such as subclinical atherosclerosis, cardiac abnormalities, hypertension, type 2 diabetes, decreased bone mineral density, renal dysfunction, obstructive sleep apnea, and polycystic ovary syndrome. Methods: We systematically reviewed PubMed; Scopus; Embase; and the Cochrane Library databases up to 28 February 2019 and assessed the quality of studies using the Newcastle-Ottawa Scale. Results: Thirty-five articles were selected for this systematic review: fifteen (4627 participants) evaluated the association of NAFLD with subclinical atherosclerosis; four (969 participants) with cardiac abnormalities; two (550 participants) with hypertension; four (1328 participants) with diabetes; six (523 participants) with low bone mineral density; two (865 participants) with renal dysfunction; one with obstructive sleep apnea; and one with polycystic ovary syndrome. Most studies found that youths with NAFLD have increased features of subclinical atherosclerosis; as well as of cardiac alterations. Limited data were available to endorse a solid estimate of the prevalence of diabetes; low mineral density and renal dysfunction in the pediatric NAFLD population. Conclusion: NAFLD-related intermediate CVD outcomes can occur and be detected early in young populations.

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          Most cited references78

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          Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

          Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9×10−10) and with hepatic inflammation (P=3.7×10−4). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
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            ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.

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              Diagnosis and management of childhood obstructive sleep apnea syndrome.

              This technical report describes the procedures involved in developing recommendations on the management of childhood obstructive sleep apnea syndrome (OSAS). The literature from 1999 through 2011 was evaluated. A total of 3166 titles were reviewed, of which 350 provided relevant data. Most articles were level II through IV. The prevalence of OSAS ranged from 0% to 5.7%, with obesity being an independent risk factor. OSAS was associated with cardiovascular, growth, and neurobehavioral abnormalities and possibly inflammation. Most diagnostic screening tests had low sensitivity and specificity. Treatment of OSAS resulted in improvements in behavior and attention and likely improvement in cognitive abilities. Primary treatment is adenotonsillectomy (AT). Data were insufficient to recommend specific surgical techniques; however, children undergoing partial tonsillectomy should be monitored for possible recurrence of OSAS. Although OSAS improved postoperatively, the proportion of patients who had residual OSAS ranged from 13% to 29% in low-risk populations to 73% when obese children were included and stricter polysomnographic criteria were used. Nevertheless, OSAS may improve after AT even in obese children, thus supporting surgery as a reasonable initial treatment. A significant number of obese patients required intubation or continuous positive airway pressure (CPAP) postoperatively, which reinforces the need for inpatient observation. CPAP was effective in the treatment of OSAS, but adherence is a major barrier. For this reason, CPAP is not recommended as first-line therapy for OSAS when AT is an option. Intranasal steroids may ameliorate mild OSAS, but follow-up is needed. Data were insufficient to recommend rapid maxillary expansion.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                17 June 2019
                June 2019
                : 8
                : 6
                : 868
                Affiliations
                [1 ]Department of Pediatrics, Sapienza University of Rome, 00161 Rome, Italy; francescomassimo.perla@ 123456uniroma1.it (F.M.P); mario.roggini@ 123456uniroma1.it (M.R.); gianmarcoandreoli@ 123456gmail.com (G.A.); m.davanzo@ 123456policlinicoumberto1.it (M.D.)
                [2 ]Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy; claudio.chiesa@ 123456ift.cnr.it
                Author notes
                [* ]Correspondence: lucia.pacifico@ 123456uniroma1.it ; Tel.: +39-06-49979215; Fax: +39-06-49979216
                Author information
                https://orcid.org/0000-0001-8136-7274
                https://orcid.org/0000-0003-3617-5630
                Article
                jcm-08-00868
                10.3390/jcm8060868
                6617181
                31213030
                4e87b47c-0231-4006-952a-2916c347a375
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 April 2019
                : 13 June 2019
                Categories
                Review

                nafld,subclinical atherosclerosis,cardiac structural and functional abnormalities,hypertension,type 2 diabetes,decreased bone mineral density,renal dysfunction,obstructive sleep apnea,polycystic ovary syndrome,children and adolescents

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