NAFLD in Children: Causes and Diagnosis
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Questions and Answers

Macrovesicular steatosis is characterized by an abnormal build-up of fat within _ cells.

liver

Cirrhosis is a reversible liver condition.

False

What is NAFLD?

Non-alcoholic fatty liver disease

What are two major factors contributing to NAFLD?

<p>Obesity</p> Signup and view all the answers

Match the following liver conditions with their definitions:

<p>Cirrhosis = Severe condition with liver tissue replaced by scar tissue Portal hypertension = Liver damage causing blood backup and pressure rise NAFLD = Excess fat accumulation in liver not caused by alcohol Steatohepatitis = Liver inflammation due to fat buildup progressing beyond storage</p> Signup and view all the answers

What are the key differences between type 1 and type 2 NASH in pediatric NAFLD?

<p>Obesity levels, age, gender, and race/ethnicity</p> Signup and view all the answers

What is the common pattern among children in terms of NASH types?

<p>Type 2 NASH</p> Signup and view all the answers

Type 2 NASH is the only subtype of pediatric NAFLD.

<p>False</p> Signup and view all the answers

What are some distinguishable features of Type 1 NASH according to the text?

<p>Perisinusoidal fibrosis</p> Signup and view all the answers

What does Mallory hyaline represent in liver histology?

<p>Mallory hyaline represents damaged intermediate filaments within liver cells.</p> Signup and view all the answers

NAFLD can be serious even at a mild fatty liver stage.

<p>True</p> Signup and view all the answers

Where is fibrosis localized in the liver when Pericellular fibrosis occurs?

<p>zone 3</p> Signup and view all the answers

Match the histological feature with its description:

<p>Ballooning degeneration = Hepatocyte enlargement adjacent to central vein Mallory hyaline = Damaged intermediate filaments in liver cells Lobular inflammation = Inflammatory cell infiltration within lobules Pericellular fibrosis = Build-up of collagen between liver cells forming scar tissue</p> Signup and view all the answers

Study Notes

NAFLD in Children

  • Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in children.
  • Two major factors contributing to NAFLD are obesity and insulin resistance.
  • The prevalence of these factors is rapidly increasing in children worldwide, causing NAFLD to become an important problem.

Thesis Statement

  • The histological features of NAFLD in adults have been well-described, but the standard criteria for the diagnosis of NAFLD or NASH in children are underdeveloped.
  • Pediatric studies of NAFLD have described patterns of inflammation and fibrosis that differ from those reported in adults.
  • There are important differences between children and adults in the histological features associated with NASH.

Objectives

  • To define the liver biopsy findings in a large series of children with clinical features consistent with NAFLD.
  • To define distinct patterns of nonalcoholic steatohepatitis (NASH) in children.
  • To determine the prevalence of NASH in children and test its potential association.

Definition of Terms

  • NAFLD: an excess accumulation of fat in the liver that is not caused by alcohol consumption.
  • NASH: a serious liver condition that arises from NAFLD, characterized by inflammation and damage to liver cells.
  • Cirrhosis: a severe condition where healthy liver tissue is permanently replaced by scar tissue.
  • Macrovesicular steatosis: characterized by an abnormal build-up of fat within liver cells, the earliest stage of NAFLD.

Hepatocytes and Portal Hypertension

  • Hepatocytes: the powerhouses of the liver, performing vital functions such as metabolism, detoxification, protein synthesis, and bile production.
  • Portal hypertension: a condition where the liver gets damaged or blocked, causing blood to back up and pressure to rise.

Pathophysiology

  • The study of the abnormal functional changes that occur at the cellular and organ level during a disease or injury.

Materials and Methods

  • Study conducted at Children’s Hospital in San Diego, California, focusing on pediatric patients diagnosed with NAFLD between 1997 and 2003.
  • Subjects were identified retrospectively and prospectively, with written assent from subjects and consent from parents.
  • Institutional review board approvals were obtained from the University of California–San Diego and Children’s Hospital, San Diego.

Diagnostic Criteria

  • NAFLD diagnosis was made after excluding other causes of chronic hepatitis.
  • Clinical data collected included demographic details, anthropometric measures, liver chemistry results, fasting insulin, and glucose levels.

Insulin Sensitivity Assessment

  • Insulin sensitivity was assessed using two models: QUICKI and HOMA-IR.
  • QUICKI is calculated as the reciprocal of the log of fasting insulin multiplied by fasting glucose.
  • HOMA-IR is calculated as fasting insulin multiplied by fasting glucose divided by 22.5.
  • Insulin resistance was defined as QUICKI ≤ 0.339 and HOMA-IR ≥ 2.0.

Histopathology

  • Liver biopsies were performed percutaneously on the right lobe using a 15-gauge needle.
  • Biopsies were ensured to be 1.5 cm or longer in length.
  • Sections of the biopsies were stained with various techniques, including hematoxylin-eosin, periodic acid Schiff, and Masson trichrome.

Histological Features Evaluated

  • Steatosis: quantified by the percentage of hepatocytes containing macrovesicular or microvesicular fat.
  • Steatohepatitis features: such as balloon degeneration of hepatocytes, Mallory hyaline, glycogen nuclei, megamitochondria, lipogranulomas, and iron deposition.
  • Fibrosis: evaluated perisinusoidal fibrosis and portal fibrosis using METAVIR criteria.

Type 1 and Type 2 NASH

  • Type 1 NASH: characterized by steatosis with ballooning degeneration and/or perisinusoidal fibrosis, without significant portal inflammation.
  • Type 2 NASH: characterized by steatosis with portal inflammation and/or fibrosis, but without ballooning degeneration or perisinusoidal fibrosis.

Key Findings

  • 106 children participated in the study, with 92% being obese.
  • 65% of the subjects were boys, and 35% were girls.
  • 8% of the subjects had type 2 diabetes mellitus.
  • 19% had mild steatosis, 28% had moderate steatosis, and 53% had severe steatosis.
  • 83% had lipogranuloma, and 55% had glycogenated nuclei.
  • 70% had portal inflammation, and 60% had portal fibrosis.

Discussion

  • This study represents the largest biopsy series of pediatric NAFLD in 2005 and demonstrates a histological spectrum ranging from simple steatosis to NASH and cirrhosis.

  • The histological profile most commonly observed in the subjects was a combination of severe steatosis with mild portal inflammation and fibrosis.

  • Using cluster analysis, distinct histological patterns were identified, including two forms of steatohepatitis.

  • This study further determined that age, sex, race, ethnicity, and severity of obesity are all associated with steatohepatitis.### The Role of Intestinal Microflora in Obesity

  • An imbalance between Firmicutes and Bacteroids bacteria in obese individuals could be a potential therapeutic target for obesity treatment.

NAFLD in Boys vs Girls

  • NAFLD is more common in boys than in girls, with boys being more likely to have NASH Type 2.
  • Hormonal differences, specifically lower estrogen levels in boys, could contribute to this increased risk.
  • Females with PCOS are also at higher risk of NAFLD due to shared risk factors such as insulin resistance, obesity, and hyperandrogenism.

Estrogen in Fatty Liver

  • Estrogen has protective effects against NAFLD, promoting fatty acid breakdown.
  • When estrogen levels decline, women are at higher risk of NAFLD, progressing from simple steatosis to NASH.

Girls with Type 1 vs Type 2 NASH

  • Girls with Type 2 NASH are several years younger than those with Type 1 NASH and are more likely to be prepubertal with hormone profiles similar to boys with Type 2 NASH.
  • In contrast, girls with Type 1 NASH are postmenarchal, with higher estrogen levels, supporting the role of estrogen in protecting against Type 2 NASH.

Type 1 vs Type 2 NASH

  • Type 2 NASH is more common in children of Asian and Native American races, while Type 1 NASH is more common in the "White" race or those with European ancestry.

Conclusion

  • The study highlights the importance of distinguishing between Type 1 and Type 2 NASH as distinct subtypes of pediatric NAFLD.
  • Key differences between these categories include obesity levels, age, gender, and race/ethnicity.
  • The findings have important implications for the investigation of the development, genetic factors, progression, and response to treatment of nonalcoholic fatty liver disease in children.

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Description

This quiz explores Non-Alcoholic Fatty Liver Disease (NAFLD) in children, including its causes, such as obesity and insulin resistance, and the challenges of diagnosing it. Learn more about this growing health problem.

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