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OBJECTIVES: To study the diagnostic performance of the enhanced liver fibrosis score (ELF) for detecting different stages of fibrosis and its usefulness in detecting histologic response to vitamin E or metformin in children with nonalcoholic fatty liver disease who participated in the Vitamin E or Metformin for the Treatment Of NAFLD In Children (TONIC) trial. STUDY DESIGN: ELF was measured at baseline and weeks 24, 48, and 96 on sera from 166 TONIC participants. Associations between ELF with baseline and end of trial (EOT) fibrosis stages and other histologic features were assessed using χ2 tests and logistic regression models. RESULTS: ELF was significantly associated with severity of fibrosis at baseline and EOT. ELF areas under the curve for discriminating patients with clinically significant and advanced fibrosis were 0.70 (95% CI, 0.60-0.80) and 0.79 (95% CI, 0.69-0.89), respectively. A 1-unit decrease in ELF at EOT was associated with overall histologic improvement (OR, 1.86; 95% CI, 1.11-3.14; P = .02), resolution of steatohepatitis (OR, 1.88; 95% CI, 1.09-3.25; P = .02), improvement in steatosis grade (OR, 1.76; 95% CI, 1.06-2.82; P = .03), and hepatocellular ballooning (OR, 1.79; 95% CI, 1.06-3.00; P = .03), but not with improvement in fibrosis stage (OR, 1.26; 95% CI, 0.78-2.03; P = .34). CONCLUSIONS: ELF was associated with fibrosis stage in children who participated in TONIC. Although not associated with improvement in fibrosis, a decrease in ELF at EOT was associated with Nonalcoholic Steatohepatitis resolution and improvement in nonalcoholic fatty liver disease histology. ELF may be a useful noninvasive test to monitor treatment response in children with nonalcoholic fatty liver disease.
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Hipoglicemiantes/uso terapêutico , Cirrose Hepática/patologia , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Índice de Gravidade de Doença , Vitamina E/uso terapêutico , Vitaminas/uso terapêutico , Adolescente , Área Sob a Curva , Biópsia , Criança , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Modelos Logísticos , Masculino , Hepatopatia Gordurosa não Alcoólica/patologia , Razão de Chances , Curva ROC , Resultado do TratamentoRESUMO
OBJECTIVES: Adolescent pregnancy in Guatemala is a multifactorial issue contributing to maternal and child mortality as well as negative social and economic outcomes. While multiple organizations have identified this as an important area for improvement, little has been published on methods for reducing rates of adolescent pregnancy in resource-limited settings. We characterized the effects of a brief intervention on the knowledge and attitudes towards sexual health of high schoolers in a rural Guatemalan community. METHODS: We created a condensed, 2-h sexual education course, which was taught to over 500 high school students in San Juan Sacatepequez, Guatemala. Students completed pre- and post-intervention surveys assessing their knowledge about pregnancy prevention and attitudes toward contraception use. Chi-square tests were used to assess the difference between the pre- and post-intervention responses as well as the responses between male and female participants. RESULTS: Analysis of the survey results revealed significant improvements in all questions assessing knowledge regarding pregnancy prevention (p<0.01). Our pre-intervention survey revealed that male participants possessed greater knowledge regarding pregnancy prevention (p<0.01). Following the intervention, several areas of initial difference between male and female students' knowledge disappeared, including knowledge of what a contraceptive is, awareness that one sexual relation is sufficient for pregnancy, and recognition that condoms can prevent sexually transmitted infections. CONCLUSIONS: This study demonstrates that brief, school-based sexual health courses are low-resource, feasible interventions to significantly increase knowledge about contraception and sexual health in resource-limited settings and improve the disparities in knowledge between male and female participants.
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OBJECTIVE: To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. STUDY DESIGN: There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. RESULTS: The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7-07). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9-07). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. CONCLUSIONS: In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies.
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Hispânico ou Latino/genética , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
UNLABELLED: Postmenopausal women with nonalcoholic steatohepatitis are at an increased risk of hepatic fibrosis compared with premenopausal women. Whether duration of estrogen deficiency in postmenopausal state dictates an individual's fibrosis risk remains uninvestigated. We assessed the associations of age at menopause and time from menopause with fibrosis severity in postmenopausal women with nonalcoholic fatty liver disease. Data from 488 postmenopausal women with (1) histologic diagnosis of nonalcoholic fatty liver disease and (2) self-reported information on age at menopause were analyzed. The associations of premature menopause (age at menopause of <40 years) and time from menopause (age at study enrollment - age at menopause, years) with fibrosis severity (stage 0-4) were assessed using multiple ordinal logistic regression models with and without adjusting for clinical confounders. Among the participants (age at menopause 43.7 ± 8.6 years), women with premature menopause (29.3%) were younger at enrollment (P < 0.001) and used hormone replacement therapy more often (P < 0.003). After adjusting for age at enrollment, race, waist circumference standardized by body mass index, current smoking, current alcohol use, hypertension, diabetes/impaired fasting glucose, homeostatic model assessment of insulin resistance, and hormone replacement therapy, premature menopause was associated with an increased likelihood of having more severe fibrosis (adjusted cumulative odds ratio = 1.9, 95% confidence interval 1.3-2.7, P = 0.001), while time from menopause was directly associated with an increased likelihood of having more severe fibrosis (adjusted cumulative odds ratio for 5-year unit = 1.2, 95% confidence interval 1.1-1.3, P = 0.002). CONCLUSION: Duration of estrogen deficiency in postmenopausal state confers fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease. (Hepatology 2016;64:85-91).
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Estrogênios/deficiência , Fígado/patologia , Menopausa Precoce , Hepatopatia Gordurosa não Alcoólica/patologia , Pós-Menopausa , Adulto , Estudos Transversais , Feminino , Fibrose , Humanos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
OBJECTIVE: To investigate the histological spectrum of nonalcoholic fatty liver disease (NAFLD) in children with normal, mildly elevated (26-50 U/L boys, 23-44 U/L girls), or elevated (>50 U/L in boys, >44 U/L in girls) serum alanine aminotransferase (ALT) levels. STUDY DESIGN: The Nonalcoholic Steatohepatitis Clinical Research Network enrolls children aged 5-18 years with NAFLD. We analyzed baseline clinical and histological data from 91 children with suspected NAFLD and normal or mildly elevated ALT and liver biopsy analysis within 180 days of ALT measurement, and compared them with data from 392 children with elevated ALT. RESULTS: Seventeen of the 91 children with suspected NAFLD (19%) had a normal ALT level, and 74 (81%) had a mildly elevated ALT level. Overall, 45% of the biopsy specimens analyzed had steatosis ≥33%, 22% had grade ≥2 lobular inflammation, 81% had portal inflammation, 29% had ballooned hepatocytes, 35% had "suspicious/borderline" steatohepatitis, 8% had definite nonalcoholic steatohepatitis, 34% had an NAFLD activity score ≥4, and 46% had fibrosis (38% mild/moderate and 8% bridging/cirrhosis). Marked steatosis (50% vs 24%) and fibrosis (54% vs 12%) were significantly more common in the patients with mildly elevated ALT compared with those with normal ALT, with no difference in ballooning, inflammation, or NAFLD activity score ≥4 between the 2 groups. Fibrosis stage 3/4 was seen in none of the children with normal ALT, in 9% of those with mildly elevated ALT, and in 15% of those with elevated ALT. CONCLUSION: Liver biopsy specimens from children with NAFLD with normal or mildly elevated ALT levels show significant histological abnormalities, including advanced fibrosis in children with mildly elevated ALT. Thus, measurement of ALT may underestimate liver injury in NAFLD. The use of appropriate ALT cutoff levels can help identify children at risk for more severe disease.