Chronic liver disease in children 2021

Causes Diagnosis and Management of Chronic Liver Disease in Children

1. Chronic Liver Disease
in
Infants and Children
Classification, Etiology, Differential diagnosis, Specific Diseases
Prof. Imran Iqbal
Fellowship in Pediatric Neurology (Australia)
Prof of Paediatrics(2003-2018)
Prof of Pediatrics Emeritus, CHICH
Prof of Pediatrics, CIMS
Multan, Pakistan

2. (God speaking to Prophet Muhammad (PBUH)
It is not possible for the sun to overtake the moon,
nor can the night outpace the day,
and each heavenly body is floating in its own orbit
The Holy Quran; surah Yaseen36:40

3. Functions of Liver
•Glucose homeostasis (maintains blood glucose level)
•Synthetic functions –albumin, carrier proteins
•Synthesis of clotting factors
•Detoxification of drugs and toxins
•Conversion of ammonia to urea for excretion
•Bilirubin excretion (produced by breakdown of RBCs)
•Storage function –glycogen, vitamins, iron
•Blood reservoir –contains 10 % of blood volume
•Anti-infective –removal of bacteria from blood

4. Clinical Presentation
of
Chronic Liver Disease

5. Chronic Liver Disease –Definitions
•Chronic Liver Disease is seen in children of all ages
•Chronic Liver Disease –liver disease lasting more than 3 to 6
months
•Cirrhosis of Liver –fibrosis, scarring, distorted architecture
and regeneration nodules (late stage of CLD)

6. Chronic Liver Disease –Stages

7. Chronic Liver Disease –Clinical Features
•Jaundice (variable)
•Anorexia and failure to thrive
•Palmar erythema
•Hepatomegaly (left lobe)
•Splenomegaly (portal hypertension)
•Ascites (transudate)
•Portal hypertension (cirrhosis)
•Hematemesis (esophageal varices)
•Hepatic Encephalopathy (advanced disease)

8. Common Causes of Hepatomegaly in Children
•Hepatic causes:Acute Hepatitis, Chronic Liver Disease, Liver
abscess
•Infective causes: Malaria, Typhoid fever
•Cardiac causes:Heart failure (Right Heart Failure)
•Hematological causes:Hemolytic anemias, Thalassemia
Major
•Metabolic causes: Diabetes, Kwashiorkor
•Storage disorders: Glycogen Storage Disease …………….

9. Common Causes of
Hepato-Splenomegaly in Children
•Infective causes:Typhoid, Malaria, Septicemia
•Hepatic causes:Chronic liver disease, Cirrhosis of liver,
Wilson's disease
•Cardiac causes:Congestive heart failure
•Hematological causes :Thalassemia major, Hemolytic
anemias
•Neoplastic causes: Lymphoma, Acute leukemia,
Histiocystosis
•Storage disorders: Mucopolysccharidosis, Lipid storage
diseases

10. Common Causes of Ascites in Children
•Without generalized edema
•Hepatic causes:Chronic Liver Disease, Cirrhosis of Liver
•Infective causes: Tuberculosis
•With generalized edema
•Cardiac causes:Heart failure (Right Heart Failure)
•Metabolic causes: Hypoalbuminemia, Malnutrition
•Renal causes: Nephrotic syndrome

11. Specific Causes
of
Chronic Liver Disease
Infants

12. Chronic Liver Disease
Infants
•Neonatal Hepatitis
•Biliary atresia
•PFIC (Progressive Familial Intrahepatic Cholestasis)

13. Neonatal Hepatitis
•Neonatal Hepatitis is hepatitis starting in first month of life
which continues for months
•Infant has jaundice, hepatomegaly and poor weight gain
•Some cases are due to intra-uterine infection by
Cytomegalovirus, Rubella virus or Toxoplasmosis infection
•In most of the patients, cause is not known
•Liver biopsy shows formation of multinucleate giant cells
•Most of the patients develop Chronic Liver Disease
•Most of the infants are likely to recover after a few months

14. Biliary Atresia
•Biliary Atresia is complete or partial non-development of
biliary tract and gall bladder
•Presents in first few weeks of life
•Infant has jaundice and clay colored stools
•US abdomen, CT abdomen and Liver biopsy are needed to
make a diagnosis
•Supportive treatment for CLD is given
•Early operative treatment (Kasai procedure) may improve
chances of survival

15. PFIC
(Progressive Familial Intrahepatic Cholestasis)
•Progressive Familial Intrahepatic Cholestasis is a group of
genetic diseases with absence of specific proteins in the
liver for secretion of bile components
•Presents in first few weeks of life
•Infant has jaundice, pruritus and hepatomegaly
•Liver biopsy shows cholestasis and bile duct proliferation
•Supportive treatment for CLD is given
•Liver transplant may be curative

16. Specific Causes
of
Chronic Liver Disease
Children

17. Chronic Liver Disease
Children
•Common causes
•Hepatitis B
•Hepatitis C
•Wilson’s disease
•Autoimmune hepatitis
•Idiopathic (25 –30 %)
•Rare causes
•Congenital Hepatic Fibrosis (in children)
•Cystic Fibrosis (in adolescents)

18. Hepatitis B

19. Hepatitis B in Children
•Hepatitis B infection can occur in children after Perinatal
transmission, household contact with infected family members,
or after blood transfusion
•Children infected with Hepatitis B virus at birth or in early life are
likely to develop chronic infection
•Chronic Liver disease can develop in these children after a few
years
•Children may present with Chronic Liver Disease due to Hepatitis
B in the immune tolerant phase or immune active phase
•Infected children show HBsAg, HbeAg, HB DNA in blood and have
variable elevation of liver enzymes
•Anti-viral treatment of children with Hepatitis B has variable
efficacy depending on immune response of body

20. Hepatitis C

21. Hepatitis C
•Hepatitis C infection can occur in children who receive
frequent blood transfusions
•Children infected with Hepatitis C virus are initially
asymptomatic
•Hepatitis C related Chronic Liver disease progresses slowly
and can manifest after many years
•Adolescents may present with Chronic Liver Disease due to
Hepatitis C
•Infected children are anti-HCV antibobyand HCV RNA
positive and have variable elevation of liver enzymes
•Anti-viral treatment of older children with Hepatitis C is
effective and should be managed as per guidelines

22. Wilson’s Disease
Epidemiology, Etiology, Pathophysiology
Clinical Features, Management

23. Wilson’s Disease
•Wilson’s Disease is a genetic inherited disorder of copper
metabolism which is quite common in Pakistan
•Genetic transmission is autosomal recessive
•Disease is more common in first cousin marriages
•Wilson’s Disease is a multi-system disorder which often
presents with hepatic and / or neurological manifestations
•Hepatic symptoms develop earlier than neurological disease
•Usual age of presentation is 5 –15 years in children
•Wilson’s Disease can present later in life at any age

24. Case scenario
•Parents bring their 9 year child to your clinic
•Parents are first cousins and this is their oldest child
•During the last few months, child has lost weight and is inactive
most of the time
•His speech is altered and he is shows difficulty in usual
movements like writing, combing and brushing
•He has developed anorexia and yellow discoloration of eyes
during the last one month
•On general examination, jaundice is visible
•On abdominal examination, ascites and splenomegaly are present
What is the most likely diagnosis ?

25. Wilson’s Disease –Pathophysiology
•Wilson’s Disease is a disorder of copper metabolism
•There is failure to synthesize a protein that binds copper to its
carrier Ceruloplasminand excretes excess copper in the bile
•There is excess storage of copper absorbed from GIT in the liver
with development ofchronic liver disease
•Ceruloplasmin(copper binding protein) levels in the blood are
low
•Excess copper is also deposited in many other organs
•Deposition of copper in Basal Ganglia of Brain produces dystonia
and other neurological manifestations
•Copper deposits in cornea are visible as Keyser-Fleisher ring

26. Wilson’s Disease

27. Wilson’s Disease –Clinical Features
•Hepatic
•Chronic Liver Disease
•Portal hypertension
•Fulminant Hepatic Failure
•Neurological
•Dystonia
•Drooling and slurred speech
•Eyes
•Keyser-Fleisher ring (K –F ring) at the periphery of cornea

28. Wilson’s Disease –Diagnosis
•Clinical
•Hepatic manifestations
•Neurological clinical features
•Eyes
•Keyser-Fleisher ring (K –F ring)
•Investigations
•Serum Ceruloplasmin–low
•Urine Copper –increased
•Liver biopsy with estimation of liver copper content

29. Wilson’s Disease –Management
•Increase Copper excretion
•Penicillamine
•Trientine
•Reduce Copper absorption
•Oral Zinc
•Management of Chronic Liver Disease and Portal
Hypertension
•Management of Neurological Disease and dystonia

30. Wilson’s Disease –Prevention
•Primary Prevention
•Pre-marital screening (DNA analysis)
•Pre-natal Diagnosis (Chorion Villus Biopsy)
•Secondary Prevention
•Early diagnosis of suspected patients
•Screening of siblings and other children in family
•Tertiary Prevention
•Adequate Management of patients (disability limitation)

31. Autoimmune Hepatitis

32. Autoimmune Hepatitis
•Autoimmune Hepatitis is seen in older children/ adolescents
•It is more common in girls
•Etiology –development of auto-antibodies against liver cells
with chronic inflammation in liver
•Clinical Presentation –Jaundice, Hepatomegaly and clinical
features of chronic liver disease
•Diagnosis –Anti nuclear antibodies (ANA), Anti liver kidney
microsomal antibodies (anti-LKM), Liver biopsy
•Management –Steroids, Immunosuppressive medications

33. Chronic Liver Disease
Diagnosis
and
Differential Diagnosis

34. Chronic Liver Disease –Clinical Features
•Jaundice (variable)
•Anorexia and failure to thrive
•Hepatomegaly (left lobe)
•Splenomegaly (portal hypertension)
•Ascites (transudate)
•Palmar erythema
•Portal hypertension (cirrhosis)
•Hematemesis (esophageal varices)
•Hepatic Encephalopathy (advanced disease)

35. Chronic Liver Disease –Lab confirmation
•LFTs –Serum bilirubin, AST, ALT, Alkaline Phosphatase, GGT
•Serum Proteins –albumin is low
•PT, APTT (coagulation profile) –prolonged
•Serum ammonia –raised in liver failure
•US abdomen –echogenic liver
•Liver Fibroscan-fibrosis
•MRI elastography–liver fibrosis
•Liver biopsy -histology
•Endoscopy –Esophageal Varices

36. Chronic Liver Disease –Etiological diagnosis
•Viral markers –Hepatitis A IgM, HBsAg, anti-HCV and others
•Serum Ceruloplasmin, Urine copper, K –F rings
•ANA, anti-LKM antibodies
•Liver biopsy
•Gene (DNA) studies for genetic, familial disorders

37. Chronic Liver Disease
Management

38. MANAGEMENT –supportive treatment
•Adequate Nutrition –according to age
•Multi-Vitamins –Fat soluble / Water soluble
•Avoid hepato-toxic medications
•Pruritus –Ursodeoxycholicacid and antihistamines
•Ascites and Edema –Diuretics
•Monitoring of child growth and biochemical profile

39. MANAGEMENT –manage complications
•Anemia -RBCs transfusion
•Coagulopathy –Plasma transfusion
•Reduction of Portal Venous Pressure –Propranolol
•Risk of Esophageal Variceal bleeds –Endoscopic ligation
•Management of Esophageal Variceal bleeds –Octreotide
•End-stage liver disease –Liver Transplant

40. MANAGEMENT –Specific treatment
•Hepatitis B
•Hepatitis C
•Wilson disease
•Autoimmune Hepatitis
•Galactosemia
•Metabolic disorders

41. EPI Revised Schedule

42. EPI Revised Schedule