The New Kids in Town: Hepatomegaly and Silent Cholecystitis

Laredo Pediatrics & Neonatology PAFrancisco J Cervantes MD, FAAPwww.LaredoPediatrics.comOctober 26, 2013

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.

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

Height Measurement

Caution with Plotting BMI

Patient Distribution by Age and BMI

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

Facts About Diabetes 80% in our children has at least 1 close relative

with diabetes10% has one of the parents with diabetes1% has both parents with diabetesMexican American have poor tolerance to

carbohydratesAs the intake of carbohydrates increases so are

the levels of insulin, visceral fat and acanthosis.

THE GOOD NEWS: IT IS REVERSIBLE!!

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

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

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

Normal Value of Alkaline Phosphatase according to the age for Girls

Beginning of the Story

Alkaline Phospatase by Age

Liver Enzymes

Adult Unisex BMI Chart

Average Height of Hispanic Kids

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

Liver Enzymes and BMI in Boys

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.

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.

Bile Formation

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.

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

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

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

TYPES OF 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 emptyingpeople 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

Who is at risk for gallstones?

The Classic 4 F’s still apply: Female, Fertile, Forty, Fat

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

Causes of GB disease in ChildrenHistory of cardiac or abdominal surgery

Prolonged parenteral nutrition Hemolytic disease

Hepatobiliary obstructive disease Obesity

Rapid decreases in weightSystemic InfectionAcute renal failure Prolonged fasting Low calorie diet

Certain medications Organ transplant

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

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

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

This test examines the gallbladder and the ducts which connect to the liver.

DISIDA (Hepatobiliary) Scan

Acalculus Cholecystitis in Boys2011-2012

Acalculus Cholecystitis in Girls2011-2012

Screening for Fatty Liver

The most effective non-invasive method

is abdominal ultrasound

Figure 1.  Focal hepatic steatosis.

Prasad S R et al. Radiographics 2005;25:321-331

©2005 by Radiological Society of North America

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

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

SGOT (AST) in Normal BMI Boys

• 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.

BMI Male # of Patient

# U/Srequest

% Positive FL

Female # of

Patient

# U/Srequest

% 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

Fatty Liver Reported to Laredo Pediatrics & Neonatology 2003-2010

Gall Bladder disease in children

•Cholecystitis•Cholelithiasis•Sludge•Polyps•Septation•Dilated or Contracted•Non Specific Thickened Wall•Phrygian Cap

Related To:Fatty LiverFocal Fat SparingHyper echoic NodesHepatomegalySpleen EnlargementAscitesPleural FluidPancreatitisCirrhosis?

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

The making of “Foie Gras”

Geese liver and “Foie Gras”

Hepatomegaly : a fragile unprotected fatty liver?

Liver Size in Children

Liver Size by BMI Groups

Liver Size and Fatty Liver

Normal

Fatty Liver

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.

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

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, be sure to get liver size by whatever means

• When ordering liver ultrasound, request liver size• Request HB scan on persistent elevated GGT and/or bilirrubin; also consider it in strong family history of GBD

(12 cm)

(20 cm)

(10 cm)

(20 cm)