Hepatitic, biliary and pancreatic disease

Question 1

What are the three types of chronic active hepatitis?

Answer 1

1.  Chronic persistent
2.  Chronic aggressive
3.  Chronic lobular

Question 2

Which gender is more likely to develop chronic active hepatitis?

Answer 2

Females

Question 3

How long should hepatitis persist to be considered “chronic active?”

Answer 3

More than 6 months

no compromises – 6 months or it’s not chronic active

Question 4

Scattered liver problems, with necrosis near the veins, are typical of what chronic hepatitis (associated with hepatitis B)?

Answer 4

Chronic lobular hepatitis

Question 5

Spider angiomata & palmar erythema are buzzwords for what general problem?

Answer 5

Chronic liver disease

Question 6

Which pediatric patients are most likely to develop sclerosing cholangitis?

Answer 6

Those with inflammatory bowel disease

Question 7

Chronic active hepatitis is associated with what HLA types?

Answer 7

DR3 & DR4

DR3 is worse

Question 8

Why are chronic hepatitis patients at risk for a life-threatening complication during commercial air travel?

Answer 8

Low cabin pressures may lead to varix rupture

Oh, dear!

Question 9

Are patients with autoimmune liver disease at high risk for recurrence if liver transplant is attempted?

Answer 9

No

It does recur, but this is rare

Question 10

What medication is the mainstay of treatment for chronic active hepatidites?

Answer 10

Steroids

other immunosuppressives are also used

Question 11

Why are chronic active hepatitis patients at risk for rickets and neuropathy?

Answer 11

Fat-soluble vitamin deficiency is common

vitamins D & E, especially

Question 12

What hand findings go with liver cirrhosis?

3

Answer 12

1.  Palmar erythema
2.  Clubbing
3.  Dupuytren’s contractures

 (tendons on palm of

 hand draw fingers in,

 decreasing hand

 function)

Question 13

Prominent veins on the anterior abdominal wall suggest what liver problem?

Answer 13

Venous outflow obstruction

Question 14

Is congenital hepatic fibrosis a type of cirrhosis?

Answer 14

No –

Cirrhosis requires fibronodular changes following hepatocyte death

Question 15

What other organ is often abnormal in congenital hepatic fibrosis patients?

Answer 15

Kidneys

Question 16

What liver abnormalities are seen in congenital hepatic fibrosis?

(2

Answer 16

1.  Abnormal ducts persistent “duct plate”
2.  Increased fibrosis

(the lobular architecture is normal)

Question 17

What are the main complications of congenital hepatic fibrosis?

(3)

Answer 17

1.  Portal hypertension
2.  Hepatosplenomegaly
3.  Cholangitis

Question 18

What is the inheritance pattern for congenital hepatic fibrosis?

Answer 18

Recessive

Fibrosis has the same letter pattern as recessive

Question 19

Why might a congenital hepatic fibrosis patient have abnormalities on CBC?

Answer 19

Low platelets & leukopenia sometimes develop with hypersplenism

Question 20

What is the typical LFT profile for a congenital hepatic fibrosis patient?

Answer 20

Normal

Question 21

Alanine aminotransferase (ALT, SGPT)

Answer 21

Increased with damaged hepatocytes

Question 22

Aspartate aminotransferase (AST, SGOT)

Answer 22

Less sensitive than ALT for hepatic injury

Question 23

Alkaline phosphatase (AP

Answer 23

Increased in cholestatic disease; also comes from bone

Higher in children because of bone growth (can identify source through isoenzyme)

Question 24

γ-Glutamyltransferase (GGT

Answer 24

More sensitive marker for cholestasis than AP

Question 25

Prealbumin

Answer 25

Shorter half-life; may reflect more acute synthetic capabilities

Question 26

Prothrombin time (PT)

Answer 26

Reflects synthetic function as a result of short half-life of factors

Question 27

What conditions are associated with elevations of aminotransferases?

Answer 27

• Steatosis (fatty liver due to metabolic syndrome)
• Hepatocellular inflammation (hepatitis)
• Drug- or toxin-associated hepatic injury
• Hypoperfusion or hypoxia
• Passive congestion (right-sided congestive heart failure, Budd-Chiari syndrome, constrictive pericarditis)
• Nonhepatic disorders (muscular dystrophy, celiac disease, macroenzyme of aspartate aminotransferase)

Question 28

What is the most frequent cause of chronically elevated aminotransferases among children and adolescents in the United States?

Answer 28

Nonalcoholic fatty liver disease (NAFLD). The condition is most commonly associated with the metabolic syndrome in obese patients. Hepatic steatosis (abnormal lipid deposition in hepatocytes) occurs in the absence of excess alcohol intake. A main concern of the condition is that this simple benign fatty liver may progress to nonalcoholic steatohepatitis (or NASH) which involves inflammation of the liver and hepatocellular damage. This ultimately can lead to cirrhosis with possible liver failure and portal hypertension. It is unclear how and why certain children make that significant pathologic jump to marked liver disease.

Question 29

When are levels of conjugated bilirubin considered abnormal?

Answer 29

Levels > 20% of total bilirubin are considered abnormal. In significant indirect (unconjugated) hyperbilirubinemia, direct (conjugated) levels usually do not exceed 15%. The levels between 15% and 20% are thus somewhat indeterminate. Generally, direct bilirubin does not exceed more than 2 mg/dL

Question 30

What are the common causes of neonatal hepatitis?

Answer 30

Idiopathic 
Viral 
Cytomegalovirus 
Herpesviruses 
Hepatitis viruses 
Human immunodeficiency virus 
Enterovirus 
Rubella 
Adenovirus 
Bacterial

Question 31

What are the common causes of neonatal cholestasis?

Answer 31

-Bile Duct Obstruction 
Biliary atresia 
Choledochal cyst 
Neonatal sclerosing cholangitis 
Congenital hepatic fibrosis 
Cholelithiasis 
Tumor or mass
--Metabolic 
α 1 -Antitrypsin deficiency 
Tyrosinemia 
Galactosemia 
Cystic fibrosis 
Bile acid synthetic disorders 
Storage disorders 
Niemann-Pick disease 
Gaucher disease 
Lipidoses 
Peroxisomal disorders 
--Endocrine 
Hypothyroidism 
Panhypopituitarism 
Other Inherited Causes 
Alagille syndrome 
Familial intrahepatic cholestasis 
Neonatal iron storage disease 
--Toxic 
Parenteral nutrition 
Drugs 
--Cardiovascular Disorders

Question 32

What is the likelihood of chronic hepatic disease developing after acute infections with hepatitis viruses A to G?

Answer 32

• Hepatitis A: 95% recover within 1 to 2 weeks of illness; chronic disease is unusual
• Hepatitis B: > 90% of perinatally infected infants develop chronic hepatitis B infection; 25% to 50% of children who acquire the virus between 1 and 5 years of age develop chronic infection; in older children and adults, only 6% to 10% develop chronic infection
• Hepatitis C: 50% to 60% develop persistent infection
• Hepatitis D: Occurs only in patients with acute or chronic hepatitis B infection; 80% develop viral persistence
• Hepatitis E: Does not cause chronic hepatitis
• Hepatitis G: Unknown

Question 33

Other than viral hepatitis, what are other common causes of acute and chronic hepatitis in children?

Answer 33

• Metabolic and genetic disorders: Wilson disease, α 1 -antitrypsin deficiency, cystic fibrosis, steatohepatitis
• Toxic hepatitis: Drugs, hepatotoxins, radiation
• Autoimmune: Autoimmune hepatitis, primary sclerosing cholangitis: anti–smooth muscle antibody positive, anti–liver-kidney-microsomal antibody positive
• Anatomic : Cholelithiasis, choledochal cyst
• Other infectious: CMV, EBV
• Toxic: Ethanol, acetaminophen
• Other inherited: Alagille syndrome, cystic fibrosis, familial intrahepatic cholestasis

Question 34

How is α 1 -antitrypsin deficiency most likely to present in infants and children?

Answer 34

α 1 -Antitrypsin deficiency is an autosomal recessive disorder that causes lung and liver disease. In the liver, injury results from intracellular accumulation of the mutant α 1 -antitrypsin protein. In the lungs, the absence of functional α 1 -antitrypsin leads to unchecked leukocyte elastase function, resulting in destruction of the alveolar walls and eventual emphysema. The pulmonary effects take years to evolve, so lung disease rarely is present in children. More common presenting symptoms are neonatal cholestasis, hepatomegaly, and chronic hepatitis. Although most patients do not have severe disease, this can progress to cirrhosis with liver failure.

Question 35

Why is measuring the level serum level of α 1 -antitrypsin not enough to diagnose α 1 -antitrypsin deficiency?

Answer 35

α 1 -Antitrypsin is an acute phase reactant and might not be decreased in all cases of α 1 -antitrypsin deficiency. Pi typing (short for protease inhibitor typing) by electrophoresis is necessary to make the diagnosis. MM is the normal phenotype and has the highest activity; ZZ has the lowest activity and the most common association with liver disease. PiMM is the most common Pi type, with a distribution of about 87%; PiMS represents 8% and PiMZ 2%. The incidence of PiZZ ranges between 1 in 2000 and 1 in 5000.

Question 36

What is the metabolic defect in patients with Wilson disease?

Answer 36

Wilson disease is an autosomal recessive defect of copper metabolism that results in markedly increased levels of copper in many tissues, most notably the liver, basal ganglia, and cornea (Kayser-Fleischer rings). The primary defect is a mutation in the transmembrane protein ATP7B, which is key to excreting excess copper into the biliary canalicular system. The combination of markedly increased copper levels in a liver biopsy specimen, low serum ceruloplasmin, and increased urinary copper excretion strongly suggests Wilson disease.

Question 37

What are the treatments of choice for Wilson disease?

Answer 37

Copper-chelating agents. d -Penicillamine has traditionally been the drug of choice, but another chelator, trientine , has been used successfully in patients who have discontinued penicillamine because of hypersensitivity reactions. Some advocate for trientine as an alternative agent to penicillamine because trientine has a better safety profile. Zinc sulfate, which inhibits intestinal copper absorption, has also been used. Patients require a low copper diet for life.

Question 38

A 3-year-old child who experiences mild fluctuating jaundice in times of illness “just like his Uncle Kevin” is likely to have what condition?

Answer 38

Gilbert syndrome, which is due primarily to a decrease in hepatic glucuronyl transferase activity. Normally, bilirubin is disconjugated to glucuronic acid. In patients with Gilbert syndrome, the defective total conjugation results in the increased production of monoglucuronides in bile and mild elevation in serum unconjugated (indirect) bilirubin. The syndrome is inherited in an autosomal dominant fashion with incomplete penetrance (boys outnumber girls by 4 to 1). Frequency of this gene in the population is estimated at 2% to 6%. Elevations of bilirubin are noted during times of medical and physical stress, particularly fasting.

Question 39

What are the clinical findings of portal hypertension?

Answer 39

Obstruction of portal flow is manifested by two physical signs: splenomegaly and increased collateral venous circulations . Collaterals are evident on physical examination in the anus and abdominal wall and by special studies in the esophagus. Hemorrhoids may suggest collaterals, but, in older patients, these are present in high frequency without liver disease, and thus their presence has no predictive value. Dilation of the paraumbilical veins produces a rosette around the umbilicus (the caput medusae), and the dilated superficial veins of the abdominal wall are visible. A venous hum may be present in the subxiphoid region from varices in the falciform ligament.

Question 40

How does autoimmune hepatitis (AIH) typically present?

Answer 40

There are three typical patterns of presentation: (1) acute hepatitis , with nonspecific symptoms of malaise, nausea and vomiting, anorexia, jaundice, dark urine, and pale stools; (2) insidious, with progressive fatigue, relapsing jaundice, headache, and weight loss; and (3) despite no history of jaundice, patients present with complications of portal hypertension (splenomegaly, GI bleeding from varices, and weight loss). Type I AIH is more common and characterized by antineutrophil antibodies and anti–smooth muscle antibodies. Type 2 AIH is characterized by anti–liver-kidney-microsomal antibodies.

Question 41

A patient with liver failure develops confusion. Why worry?

Answer 41

Hepatic encephalopathy can appear as either a rapid progression to coma or as mild fluctuations in mental status over an extended amount of time. A single underlying cause has not been established, but suspected toxins include ammonia, other neurotoxins, and relatively increased γ-aminobutyric acid activity. Management requires the limitation of protein intake, the use of lactulose to promote mild diarrhea, antibiotics to reduce ammonia production, intracranial pressure monitoring in advanced cases, and possible peritoneal dialysis for patients in severe coma and before liver transplantation.

Question 42

What is the most common indication for pediatric liver transplantation?

Answer 42

The most common indication is extrahepatic biliary atresia with chronic liver failure after a Kasai hepatoportoenterostomy. Other common indications include inborn errors of metabolism (e.g., α 1 -antitrypsin deficiency, hereditary tyrosinemia, Wilson disease) and idiopathic fulminant hepatic failure.

Question 43

Calculous and acalculous cholecystitis: what are the differences?

Answer 43

Calculous cholecystitis : Gallstone impaction in the cystic duct results in gallbladder distention edema, biliary stasis, and bacterial overgrowth (e.g., E. coli, Klebsiella, enterococci). If untreated, this can lead to gallbladder infarction, gangrene, and perforation.

Acalculous cholecystitis: Gallbladder dysfunction results from a variety of conditions including major trauma, sepsis/hypotension, and diabetes. Bile stasis results, which can lead to an inflammatory response; ischemia; distention; and eventually, necrosis of gallbladder tissue.

Question 44

What are the possible causes of pancreatitis in children?

Answer 44

-33%: Systemic disorders (sepsis and shock, vasculitis)
• 13% to 34%: Idiopathic
• 10% to 40%: Trauma (motor vehicle accidents, sports injuries, accidental falls, child abuse)
• 10% to 30%: Biliary disease (gallstones, sludge)
•

Question 45

What is the typical presentation of acute pancreatitis in children?

Answer 45

In children > 3 years of age, the most common symptom is abdominal pain , which occurs in 80% to 95%. Pain is typically epigastric in location. Radiation to the back is uncommon. Nausea or vomiting occurs in 40% to 80%. Abdominal distention is also common. Infants and toddlers are less likely to complain of abdominal pain and nausea and are more likely to have fever.

Question 46

Which enzyme is a more sensitive marker of pancreatic injury in children: amylase or lipase?

Answer 46

There is no clear winner. In a compilation of pediatric studies, the sensitivity of the amylase test in diagnosing pancreatitis has ranged from 50% to 85%, while lipase was only marginally more sensitive than amylase in most studies. Amylase values rise 2 to 12 hours after the onset of pancreatitis; lipase values rise at 4 to 8 hours. Because only one or the other may be elevated in individual patients, both lipase and amylase should be measured in suspected pancreatitis.

Srinath AI, Lowe ME: Pediatric pancreatitis, Pediatr Rev 34:79–89, 2013.

Question 47

What conditions may be associated with hyperamylasemia?

Answer 47

Pancreatic: pancreatitis, pancreatic tumors, pancreatic duct obstruction, biliary obstruction, perforated ulcer, bowel obstruction, acute appendicitis, mesenteric ischemia, endoscopic retrograde cholangiopancreatogram (ERCP)
Salivary: infections (mumps), trauma, salivary duct obstruction, lung cancer, ovarian tumors or cysts, prostate tumors, DKA
Mixed or unknown: cystic fibrosis, renal insufficiency, pregnancy, cerebral edema, burns