In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis

Africa, Jonathan A.; Behling, Cynthia; Brunt, Elizabeth M.; Zhang, Nan; Luo, Yunjun; Wells, Adam J.; Hou, Jiayi; Belt, Patricia; Kohil, Rohit; Lavine, Joel E.; Molleston, Jean P.; Newton, Kimberly P.; Whitington, Peter F.; Schwimmer, Jeffrey B.

doi:10.1016/j.cgh.2017.02.030

Cited by 56 publications

(54 citation statements)

References 24 publications

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“…In many cases of pediatric NAFLD, particularly in boys, steatosis may be accentuated in the periportal regions. These differences in pattern have been informative in developing an understanding of pediatric NAFLD, discussed below . Another example commonly found in liver biopsies for numerous clinical indications is portal chronic inflammation.…”

Section: Liver Biopsy Evaluation In Nafld: Methods For Assessmentmentioning

confidence: 99%

“…These differences in pattern have been informative in developing an understanding of pediatric NAFLD, discussed below. (61)(62)(63) Another example commonly found in liver biopsies for numerous clinical indications is portal chronic inflammation. This lesion is not present in either the NAS or the SAF/FLIP algorithm for scoring (or diagnosing) NASH but is usually present to some extent in NAFLD.…”

Section: Liver Biopsy Evaluation In Nafld: Methods For Assessmentmentioning

confidence: 99%

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Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation

Brunt¹

2017

Hepatology Communications

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Nonalcoholic fatty liver disease (NAFLD) is one of the most common underlying causes of chronically elevated liver tests and liver disease in adults and children worldwide and may be strongly suspected if not diagnosed by ever evolving and available serologic and imaging‐based noninvasive tests. However, the definitive diagnosis of the most progressive form of NAFLD, nonalcoholic steatohepatitis, and the identification of fibrosis stage still require liver biopsy evaluation as noninvasive testing has not replaced some of the specifics or the totality of information obtainable from liver biopsy. In this review, both the role and value of a liver biopsy evaluation in NAFLD/ nonalcoholic steatohepatitis are examined from publications related to a selected variety of settings. Details of the most commonly used semiquantitative methods of analysis are discussed, and some useful potential pitfalls for differential diagnostic consideration in liver biopsy interpretation are given. (Hepatology Communications 2017;1:370–378)

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Section: Liver Biopsy Evaluation In Nafld: Methods For Assessmentmentioning

confidence: 99%

Section: Liver Biopsy Evaluation In Nafld: Methods For Assessmentmentioning

confidence: 99%

Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation

Brunt¹

2017

Hepatology Communications

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“…Furthermore, the well‐known differing histological patterns in paediatric NAFLD, presenting with a portal/zone 1‐predominant type or an “adult” zone 3‐predominant type, suggest a distinct genetic impact on the development of disease . This phenomenon is of particular importance, since the portal/zone 1 pattern is more frequent in younger children and associated with an increased risk of advanced fibrosis . Genetic variants associated with the portal/zone 1‐predominant type in paediatric NAFLD have not yet been identified.…”

Section: Introductionmentioning

confidence: 99%

“…9 This phenomenon is of particular importance, since the portal/zone 1 pattern is more frequent in younger children and associated with an increased risk of advanced fibrosis. 10,11 Genetic variants associated with the portal/zone 1-predominant type in paediatric NAFLD have not yet been identified.…”

Section: Introductionmentioning

confidence: 99%

Genetic determinants of steatosis and fibrosis progression in paediatric non‐alcoholic fatty liver disease

Hudert

Selinski

Rudolph

et al. 2018

Liver International

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Background and Aims Non‐alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents today. In comparison with adult disease, paediatric NAFLD may show a periportal localization, which is associated with advanced fibrosis. This study aimed to assess the role of genetic risk variants for histological disease pattern and severity in childhood NAFLD. Methods We studied 14 single nucleotide polymorphisms (SNP) in a cohort of 70 adolescents with biopsy‐proven NAFLD. Genotype was compared to an adult control cohort (n = 200) and analysed in relation to histological disease severity and liver tissue proteomics. Results Three of the 14 SNPs were significantly associated with paediatric NAFLD after FDR adjustment, rs738409 (PNPLA3, P = 2.80 × 10−06), rs1044498 (ENPP1, P = 0.0091) and rs780094 (GCKR, P = 0.0281). The severity of steatosis was critically associated with rs738409 (OR=3.25; 95% CI: 1.72‐6.52, FDR‐adjusted P = 0.0070). The strongest variants associated with severity of fibrosis were rs1260326, rs780094 (both GCKR) and rs659366 (UCP2). PNPLA3 was associated with a portal pattern of steatosis, inflammation and fibrosis. Proteome profiling revealed decreasing levels of GCKR protein with increasing carriage of the rs1260326/rs780094 minor alleles and downregulation of the retinol pathway in rs738409 G/G carriers. Computational metabolic modelling highlighted functional relevance of PNPLA3, GCKR and UCP2 for NAFLD development. Conclusions This study provides evidence for the role of PNPLA3 as a determinant of portal NAFLD localization and severity of portal fibrosis in children and adolescents, the risk variant being associated with an impaired hepatic retinol metabolism.

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“…Similarly in agreement with other published data involving older groups of Japanese 39 , age is strongly associated with the development and progression of NASH 33 . However, this agreement does not preclude the observation that in children with NAFLD, steatosis is associated with advanced fibrosis as indicated in the latest published report 40 . Other reports also indicate that DM is associated with NASH in older male NAFLD group whereas a higher frequency of advanced fibrosis was observed in an older female NASH group.…”

Section: Discussionmentioning

confidence: 77%

Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C

et al. 2017

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Background & Aim Several factors involved in the development of liver fibrosis in African American patients with chronic hepatitis C (CHC) have not been well-studied. We aimed to evaluate some of these risk factors. Methods We reviewed pathology and medical records of 603 African Americans with chronic hepatitis C virus (HCV) infection at Howard University Hospital from Jan. 2004 to Dec. 2013. Among the clinical and pathological data collected were HIV (human immunodeficiency virus), HCV genotype, Hepatitis B virus (HBV), diabetes mellitus (DM), hypertension (HTN), body mass index (BMI), and hepatic steatosis. Results The frequency of DM, HTN, HIV and HBV were 22%, 16%, 11%, and 4%, respectively. Median BMI was 27.3 kg/m2. The frequency of fibrosis stages 0, 1, 2, 3 and 4 were 2%, 48%, 28%, 11% and 11%, respectively. In multivariate logistic regression, we found a significant association between liver fibrosis stage (3–4 vs. 0–2) and HIV infection (OR=2.4, P = 0.026), hypertension (OR=3.0, P = 0.001), age (OR=2.6 for every 10 years, P<0.001), weight (OR = 1.1 for every 10 pound increase, P = 0.002) and steatosis grade (OR = 1.6, P = 0.002). The frequency of liver steatosis was 73%. In an ordinal logistic regression, significant risk factors for steatosis were female gender (OR = 1.5, P = 0.034) and inflammation grade (P=0.001). Conclusion This study shows that steatosis is independently associated with fibrosis in African American patients with HCV infection. Female patients were at higher risk for steatosis.

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In Children With Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis Is Associated With Advanced Fibrosis

Cited by 56 publications

References 24 publications

Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation

Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation

Genetic determinants of steatosis and fibrosis progression in paediatric non‐alcoholic fatty liver disease

Clinical and Pathological Risk Factors Associated with Liver Fibrosis and Steatosis in African-Americans with Chronic Hepatitis C

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