1. Hepatomagaly in children Prof. Dr. Cengiz Canpolat Department of Pediatrics Division of Pediatric Hematology- Oncology

2. Liver The liver is an important organ located in the upper right quadrant of the abdomen. It is responsible for: Filtering the blood Making bile, a substance that helps digest fat and excrete certain fatty substances Processing and hooking fats to carriers (including cholesterol), and storing sugars, helping the body transport and save energy Making important proteins, such as most of those involved in blood clotting Metabolizing many medications, such as barbiturates, sedatives, and amphetamines Storing iron, copper, vitamins A and D, and several of the B vitamins Making important proteins like albumin that regulate fluid transport in the blood and kidneys Helping break down and recycle red blood cells

3. Hepatomagaly in children Liver size may be estimated by degree of extension of liver edge below right costal margin or by span of liver dullness to percussion In children liver edge may be normally palpable up to 2 cm below right costal margin. However, this assessment of liver size may be unreliable if other non-hepatic factors (e.g.,lung disease) push diaphragm lower and thus the liver below the costal margin

4. Hepatomagaly in children Liver span is a more reliable measurement of liver size. It is the distance determined by percussion between upper margin of liver dullness and its lower edge. Span of 5–7cm is normal in infants and children, whereas 8–10 cm is normal in adolescents

5. Hepatomagaly in children Signs and symptoms of enlarged liver: Tenderness. If the liver enlarges quickly, it may be tender to the touch Pain. A markedly enlarged liver may cause abdominal pain or fullness Jaundice. If the cause of enlargement affects liver function, it may lead to yellowing of the skin (jaundice)

6. Principle causes of hepatomagaly Infection/inflammation 1-Hepatitis Viral (TORCH) Bacterial (septicemia, endocarditis, brucellosis,leptospirosis, cat scratch disease, tuberculosis, and liver abscess) Other infections :Rickettsial (Rocky Mountain spotted fever),fungal (histoplasmosis, coccidioidomycosis), and parasitic (malaria,amebiasis, toxoplasmosis, ascariasis, schistosomiasis, toxocariasis) Toxic, drug ( high doses of vitamins like A and D, prolonged use of acetaminophen, certain antibiotics, steroids ) Autoimmune 2-Cholangitis (biliary obstruction)

7. Principle causes of hepatomagaly Hemolytic anemia (HS, SCD, Thalassemia) Cardiac disorders (right-sided CHF) Trauma Bile duct obstruction – Biliary atresia – Caroli disease

8. Principle causes of hepatomagaly Vascular disorders – Budd-Chiari syndrome – Venoocclusive disease Neoplasia (leukemia, lymphoma, metastatic cancer, hepatoblastoma, HCC) Metabolic disorders – Disordersof carbohydrate metabolism Galactosemia Hereditary fructose intolerance Glycogen storage disease – Glycogenstorage disease type I – Glycogen storage disease type III – Glycogen storage disease type IV – Glycogen storage disease type VI

9. Principle causes of hepatomagaly – Disorders of amino acid metabolism Tyrosinemia Urea cycle defects – Disorders of lysosomal storage Mucopolysaccharidoses Lipidoses – Gaucher disease (Types I, II, III) – Nieman-Pick disease (Types A, B, C) – GM-1 gangliosidosis – GM-2 gangliosidosis (Sandhoff disease) Glycoprotein disorders – Fucosidosis(Types I, II) – Sialidosis type II Wolman disease and cholesterol esterdisease

10. Principle causes of hepatomagaly – Disorders of fatty acid oxidation – Disorders of bile acid synthesis and transport – Alpha1-antitrypsin deficiency (a genetic liver disease in children that can lead to hepatitis and cirrhosis of the liver ) – Wilson disease (an inherited condition that causes a build up of the mineral copper in the liver ) – Reye syndrome (a condition that causes a build up of fat in the liver, linked in some cases to use of aspirin, especially in conjunction with chickenpox, influenza, or other illnesses with fever) – Zellweger syndrome

11. Principle causes of hepatomagaly Systemic disorders – Obesity (fat accumulation in liver Serum bilirubin is usually normal, whereas serum aminotransferases and alkaline phosphatase may be increased) – Diabetes mellitus ( fat accumulation or increased glycogen stores) – Cystic fibrosis ( fat accumulation, focaland multilobular biliary cirrhosis, portal hypertension, and cholelithiasis) – Malnutrition (fat accumulation) – Connective tissue diseases (SLE, JRA) – Histiocytoses – Total parenteral nutrition (cholestasis is main response in infants, whereas older children develop fat accumulation and hepatitis)

12. Clinical presentation Hepatomegaly can occur as isolated finding with or without splenomegaly, with jaundice, with significant increase in serum aminotransferases, in association with systemic disorders, with persistent vomiting and altered consciousness, or with progressive neurologic deterioration

13. Approach to the diagnosis Shortness of breath, pitting edema, and hepatomegaly suggest CHF Chronic cough, wheezing, jugular vein distention, hepatomegaly, and pitting edema suggest pulmonary emphysema and cor pulmonale Fever, tender hepatomegaly, and jaundice suggest viral hepatitis or cholangitis Hepatomagaly and ascites suggest cirrhosis

14. Approach to the diagnosis History –Abdominal pain, fever, melena, weight loss, medications, age at onset, diarrhea, vomiting, hematemesis, bleeding, bruising, fatigue –Exposure to blood products –Nutrition history (neonatal formula) –Travel history to endemic infectious areas –Family history of liver disease, hemolytic anemia, maternal HBV, HCV -delayed development -carbohydrate/lipid storage diseases -difficulty in feeding, dyspnea-cardiac disorders -fever- Malaria, Kala-azar, TB, malignancy

15. Approach to the diagnosis Age at onset- Appearance in neonatal period: -congestive heart failure (right sided) -intrauterine infections and neonatal hepatitis -isoimmunization disorders -hemolytic anaemias -congenital syphilis -Maternal diabetes -Biliary atresia -antitrypsin deficiency

16. Approach to the diagnosis Appearance in infancy with prominent systemic findings; -Beta-thalassemia major -Sickle cell disease -Glycogen storage diseases -Mucopolysaccharidosis

17. Approach to the diagnosis Appearance in first decade without apparent chronic illness; -Iron deficiency -Hepatoblastoma -Homocystinuria -Congenital lipodystrophy -Type I Hyperlipoproteinemia.

18. Approach to the diagnosis Appearance in 1st decade with apparent illness; -Hemolytic anaemias -Indian childhood cirrhosis (preschool age group) -Chediak - Higashi syndrome -Chronic granulomatous disease -Metastatic tumours

19. Approach to the diagnosis Appearance at any age, relatively asymptomatic; -Cirrhosis -Ascariasis (migration into the liver) -Inflammatory bowel disease -Polycystic disease of liver -Hepatic tumours -Hydatid disease?

20. Approach to the diagnosis Appearance at any age, 'sick' child: -Malaria, -Sepsis, -Enteric fever, -Hepatitis, Congestive cardiac failure, Tuberculosis, Kwashiorkor, leukaemia & lymphoma -Liver abscess - amoebic & bacterial -Juvenile RA & SLE -Drugs & toxins - Phenobarbitone,acetaminophen, sulfonamides, tetracyclines,steroids, etc. -Alpha 1- antitrypsin deficiency -Wilson's disease

21. Approach to the diagnosis Physical exam –Height, weight –Liver size, margin, firmness, nodularity, tenderness –Ascites, jaundice/scleral icterus –Cataracts; Kayser-Fleischer rings (Wilson) –Cardiac exam for murmurs; splenomegaly; tone and strength development; hemangiomas/xanthomas

22. Approach to the diagnosis General examination : -Pallor - Malaria, hemolytic anaemia, hematological malignancy -Petechia, purpura, ecchymosis, lymphadenopathy - Leukemia -Jaundice - intrauterine infections, septicemia, neonatal hepatitis, viral hepatitis, biliary atresia -Spider nevi, icterus, flaps - Hepatic failure -features of PEM - Kwashiorkor

23. Approach to the diagnosis -Microcephaly - Intrauterine infections (Toxoplasmosis, CMV) -Mental retardation - Mucopolysaccharoidosis, galactosemia -Eyes - Cataract in galactosemia, Kayser - Fleischer ring over the cornea in Wilson's disease -Hazy cornea - Mucopolysaccharoidosis -Skin rash - Histiocytosis -Skeletal changes of rickets - Cystinosis & tyrosinosis

24. Approach to the diagnosis Labs –CBC, ALT, AST, fractionated bilirubin, alkaline phosphatase, total protein, albumin, globulin fraction, U/A –Hepatitis serologies, EBV, TORCH titers, plasma amino acids/urine organic acids for metabolic disease –Serum A1AT with protease inhibitor typing –Ceruloplasmin (decreased in Wilson disease) –ANA/anti-smooth muscle antibody/anti-liver kidney microsomal antibody, IgG for autoimmune hepatitis

25. Approach to the diagnosis Febrile agglutinins (typhoid fever, brucellosis) Monospot test (infectious mononucleosis) Serum iron and iron-binding capacity (hemochromatosis) Stool for occult blood (metastatic malignancy) Stool for ova and parasites (amebic abscess, cysticercosis and other parasites) Bone marrow examination (hemolytic anemias, leukemia, myeloid metaplasia)

26. Approach to the diagnosis GI series and barium enema (metastatic neoplasm) Sonogram (hepatic cyst, gallstones, abscess) Laparoscopy (cirrhosis, metastatic neoplasm) Liver biopsy (cirrhosis, hepatitis, metastatic carcinoma) Serum α-fetoprotein (hepatoma) Mitochondrial antibody titer (biliary cirrhosis)

27. Thank you for your attention