This document summarizes a presentation on hepatomegaly (enlarged liver) and silent cholecystitis (gallbladder inflammation without symptoms) in children. It discusses risk factors for these conditions like being overweight, rapid weight changes, and family history. Laboratory tests and imaging like ultrasound and HIDA scans are used to identify fatty liver, gallstones, gallbladder sludge, and other issues. The rates of fatty liver and gallbladder disease appear to be increasing in children, associated with rising childhood obesity. Early detection is important as fatty liver can progress rapidly in children.

1. The New Kids in Town: Hepatomegaly
and Silent Cholecystitis
Laredo Pediatrics & Neonatology PA
Francisco J Cervantes MD, FAAP
www.LaredoPediatrics.com
October 26, 2013

2. Conflict of Interest Disclosure
Francisco J Cervantes MD:
I or any on my immediate family have no
Financial interest/arrangement or affiliation
with any organization that could be perceived
as real or apparent conflict of interest.

3. OBJECTIVES
At the end of the presentation you will be provided
with enough information to identify:
• Children at risk of developing Cholecystitis
and/or Hepatomegaly
• Laboratory values that suggest Cholecystitis
and/or Hepatomegaly
• Indications to order Liver U/S vs. HB Scan

4. Height Measurement

5. Caution with Plotting BMI

6. Patient Distribution by Age and BMI

7. A Rational Approach
During 2001 we recommended the SAD Diet
(Standard American Diabetes Association) low fat,
high Carbs. It didn't work
August 2002: Modified Diet, basically: lower sugar
intake, more protein and vegetables, diet drinks
or water. Blood work and diet recommended at
school to Overweight kids and close f/u
September 2003: Results of First 1000 classified
patients
April 2004: Update to 3000 patients

8. Facts About Diabetes
 80% in our children has at least 1 close
relative with diabetes
10% has one of the parents with diabetes
1% has both parents with diabetes
Mexican American have poor tolerance to
carbohydrates
As the intake of carbohydrates increases so
are the levels of insulin, visceral fat and
acanthosis.
THE GOOD NEWS: IT IS REVERSIBLE!!

9. Screening
• CMP, GGT, Lipid profile, Liver Function Test:
Alkaline phosphatase, ALT, AST, Bilirubin,
• HbA1c, Insulin, THS and T4
• Biometric information; Weight, Height, BMI,
Waist and hip circumference and Percentage of
body fat
• Blood pressure
• Ultrasound of the liver if altered liver enzymes, or
complaining of RUQ pain or discomfort

11. Local Experience
•2116 patients, about equally divided,
boys (1041, 49.2%) and girls (1075, 50.8%)
•First generation American-born children of
Hispanic descend.
•Patients were followed because of changes in
BMI then the discovery of the fatty liver and
subsequently Gallbladder disease.
• All patients have at least one metabolic screen.
•BMI groups normal BMI 75, 85, 95,97 and ≥99
WWW.Laredopediatrics.com

12. Criteria for screening for liver disease
• Persistent Overweight BMI 85 to 90 %tile
• BMI above 95 %tile
• Rapid Increase in BMI no matter where it
starts
• Family history of Lipid disorder, liver or
gallbladder disease and Diabetes
• RUQ or epigastric discomfort

16. Normal Value of Alkaline Phosphatase
according to the age for Girls

17. Beginning of the Story

18. Alkaline Phospatase by Age

19. Liver Enzymes

21. Adult Unisex BMI Chart

22. Average Height of Hispanic Boys

23. Average Height of Hispanic Girls

24. Difference Between The Four Subgroups of Normal BMI
Boys 240 Girls 223
n 50 35 60 95 18 29 54 122
10 25 50 75 10 25 50 75
Glucose ↑ ↑
↑
10/25 50 10/25
Insulin ↑ ↑
↑
10 25 25
HDL
↑
↑
50 50
TGL
↑
↑
50 50
28th Annual Update In Medicine conference Oct.2012
March 2013

26. Liver Enzymes and BMI in Boys

29. Bile Formation
The liver's cells (hepatocytes) excrete bile into
canaliculi, which are intercellular spaces
between the liver cells. These drain into the
right and left hepatic ducts, after which bile
travels via the common hepatic and cystic
ducts to the gallbladder.
The gallbladder, which has a capacity of 50
milliliters (about 5 tablespoons),
concentrates the bile 10 fold by removing
water and stores it until a person eats. At
this time, bile is discharged from the
gallbladder via the cystic duct into the
common bile duct and then into the
duodenum (the first part of the small
intestine), where it begins to dissolve the
fat in ingested food.

30. Synthesis of bile acids is a major route
of cholesterol metabolism in most
species other than humans.
The Liver produces about 800 mg of
cholesterol per day and about half of
that is used for bile acid synthesis.
20-30 grams of bile acids are secreted.
90% of excreted bile acids are
reabsorbed by in the ileum.
Bile is also used to break down fat
globules into tiny droplets.

31. Pathophysiology of Gall bladder
disease
• Cholecystitis calculous and Acalculous.
• In the pediatric population most gallbladders that are
removed for acute cholecystitis show evidence of chronic
inflammation.
• Mechanism of Chronic Inflammation :
cholesterol crystals and/or calcium bilirubinate→ stone
→inflammation→ chronic obstruction→ decreased
contractile → biliary stasis→ Inflammation of the
gallbladder wall

32. Pathophysiology of Gall bladder
disease
• Acalculus Cholecystitis:
similar manner but from different etiologic most
often associated with systemic illness or
infection→ Increased mucous production,
dehydration, and increased pigment → increase
cholesterol saturation and biliary stasis→
hypofunction→ biliary sludge → obstruction →
inflammation, edema → compromised blood flow
and bacterial infection

33. TYPES OF GALLSTONES
The two types of gallstones are cholesterol stones
and pigment stones. Cholesterol stones are usually
yellow-green and are made primarily of hardened
cholesterol. They account for about 80 percent of
gallstones. Pigment stones are small, dark stones
made of bilirubin. Gallstones can be as small as a
grain of sand or as large as a golf ball. The gallbladder
can develop just one large stone, hundreds of tiny
stones, or a combination of the two

34. Who is at risk for gallstones?
women—especially pregnant, use of hormone replacement
therapy, or birth control pills (decrease gallbladder movement)
people over age 60 (As people age, the body tends to secrete more
cholesterol into bile)
American Indians (Pima Indians of Arizona, 70% of women have
gallstones by age 30)
Mexican Americans
overweight or obese ( Bile salts Cholesterol GB emptying
people who fast or lose a lot of weight quickly
people with a family history of gallstones (possible genetic link)
people with diabetes (high levels of fatty acids called triglycerides)
people who take cholesterol-lowering drugs
The Classic 4 F’s still apply: Female, Fertile, Forty, Fat

35. Criteria for screening for Gall bladder disease
•Persistently Abnormal liver enzymes
•Acute or persistent epigastric or non-specific
abdominal pain, postprandial
•Rapid decline in BMI
•Family history of Gall bladder disease
• persistently elevated GGT or Total
Bilirrubin

36. Causes of GB disease in Children
History of cardiac or abdominal surgery
Prolonged parenteral nutrition
Hemolytic disease
Hepatobiliary obstructive disease
Obesity
Rapid decreases in weight
Systemic Infection
Acute renal failure
Prolonged fasting
Low calorie diet
Certain medications
Organ transplant

37. Signs and Symptoms
• Typical symptoms of RUQ pain, nausea, vomiting.
• Tenderness to palpation or mass at RUQ
• Leukocytosis and jaundice
• The pain and tenderness are less localized in younger
children
• Epigastric pain mimic RUQ pain
• Epigastric pain or discomfort postprandial
• Atypical presentation: Sleep apnea and sleep
disturbance

38. Surgical Gallbladder Cases
• 404 in 4,000,000 in 4 years = 1 in 40,000 per
year at Texas Children’s Houston (2005-2008)
73% women
• 11 in 2000 in 1 yr = 1 in 200 per year at Laredo
Pediatrics (2010 -2011) 63% women
• 8 other reported at local pediatric meetings

41. Normal Findings of HB Scan
• Hepatocytes take up the
radiopharmaceutical in minutes after
injection
• Hepatic ducts seen in fifteen minutes
• Gallbladder seen within 45 to 60 minutes
• GBEF >40
• Small intestine seen by 30 minutes

43. DISIDA (Hepatobiliary) Scan
This test examines the gallbladder and the ducts which connect to the liver.

44. Acalculus Cholecystitis in Boys
2011-2012

46. Acalculus Cholecystitis in Girls
2011-2012

51. Screening for Fatty Liver
The most effective
non-invasive method
is abdominal
ultrasound

52. Figure 1. Focal hepatic steatosis.
Prasad S R et al. Radiographics 2005;25:321-331
©2005 by Radiological Society of North America

53. Figure 7. Focal fat accumulation in the liver at US. Transverse image shows, adjacent to the
left portal vein, a geographically shaped area of high echogenicity that represents
accumulation of fat (f) in the falciform ligament, with posterior acoustic attenuation.
Hamer O W et al. Radiographics 2006;26:1637-1653
©2006 by Radiological Society of North America

54. Figure 4. Diffuse fat accumulation in the liver at US. The echogenicity of the liver is greater
than that of the renal cortex (rc).
Hamer O W et al. Radiographics 2006;26:1637-1653
©2006 by Radiological Society of North America

55. SGOT (AST) in Normal BMI Boys

56. • Ultrasound of the liver shows centrilobular or starry sky pattern characterized by increased
brightness portal venules and diminished parenchymal echogenicity accentuating the portal venule
walls. Acute hepatitis is the most common cause of starry sky appearance. This sonographic
appearance is due to the intralobular edematous swelling of the hepatocytes and a change in
acoustic properties between the portal venous radicals and hepatic lobules.

57. Fatty Liver Reported to Laredo Pediatrics & Neonatology
BMI Male
# of Patient
# U/S
request
2003-2010
% Positive
FL
Female
# of
Patient
# U/S
request
% Positive
FL
NR 158 6 0 199 9 0
Risk 191 41 36.6 263 26 23.0
≥ 95 132 31 45.2 105 25 40.0
≥ 97 234 92 45.5 200 59 54.2
≥ 99 210 105 55.2 132 73 46.6
Total 925 275 50.5 899 192 42.7

58. Gall Bladder disease in children
•Cholecystitis
•Cholelithiasis
•Sludge
•Polyps
•Septation
•Dilated or Contracted
•Non Specific Thickened
Wall
•Phrygian Cap
Related To:
Fatty Liver
Focal Fat Sparing
Hyper echoic Nodes
Hepatomegaly
Spleen Enlargement
Ascites
Pleural Fluid
Pancreatitis
Cirrhosis?

61. Foie gras
• French for "fat liver" is a food product made of
the liver of a duck or goose that has been
specially fattened.
• By French law, foie gras is defined as the liver
of a duck or goose fattened by force-feeding
corn with a gavage, although outside of France
it is occasionally produced using natural
feeding

62. The making of “Foie Gras”

63. Geese liver and “Foie Gras”

64. Hepatomegaly : a fragile
unprotected fatty liver?

65. Liver Size in Children

66. Liver Size by BMI Groups

68. Liver Size and Fatty Liver
Normal
Fatty Liver

69. Conclusion
•The Latest data suggest that 16% of children in
the United States are obese and 32% are
overweight. Therefore concern about prevalence
of NAFLD or NASH is appropriate
•The studies recognized rapid progression of
fibrosis in children with NAFLD/NASH over short
period of time. Therefore early detection is
warrant
•Although gallbladder disease is relatively
uncommon in the pediatric population, the rate
has increased in the past 10 years.
•Pediatric gallbladder disease was commonly
associated with hemolytic diseases or
hemoglobinopathies; however, now other factors
are recognized.

70. Conclusion
•Incidence of Gallbladder disease is on the rise on
overweight children.
•Gallbladder disease should be in the differential
diagnosis of any pediatric patient who presents with
localized pain in the epigastric, RUQ or ill-defined,
Jaundice or dyspepsia and asymptomatic patients with
BMI of ≥85
•Consider Liver ultrasound as primary tool over
more expensive and invasive procedures
•HB Scan helps identify adequate GB function

71. Recommendations
• When clearing Young athletes:
– consider where do they stand in the BMI scale
– Overweight carries higher risk for injuries
– On Obese athletes don’t forget the fragile
unprotected fatty liver at risk of rupture
• When Ordering Liver Ultrasound, request Liver
size
• Request HB Scan on persistent elevated GGT
and bilirrubin

72. QUESTIONS?.........